QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Abstract Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhuang, X. Articles by Hen, R. Search for Related Content PubMed PubMed Citation Articles by Zhuang, X. Articles by Hen, R. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB COCAINE DOPAMINE

Next Article 

The Journal of Neuroscience, 2000, 20:RC91:1-5

RAPID COMMUNICATION
G_OLF Mediates Dopamine D₁ Receptor Signaling

Xiaoxi Zhuang, Leonardo Belluscio, and Rene Hen

Center for Neurobiology and Behavior, Columbia University, New York, New York 10032

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERALS AND METHODS RESULTS DISCUSSION REFERENCES

It is generally assumed that the coupling of dopamine D₁ receptors to adenylyl cyclase is mediated by the stimulatory GTP-binding protein G_s. However, the striatum contains little G_s subunit, whereas it expresses high levels of G_olf, a close relative of G_s that is also expressed in olfactory receptor neurons. We used G_olf knockout mice to examine the functional coupling of D₁ receptors. We found that these mice showed no hyperlocomotor response to either the D₁ agonist SKF-81297 or the psychostimulant cocaine. Moreover, G_olf knockout mice did not display cocaine-induced c-fos expression in the striatum. Finally, in the absence of G_olf, striatal D₁ receptors have a decreased affinity for dopamine. Thus coupling to G_olf appears to mediate D₁ signaling in the striatum.

Key words: dopamine; D₁ receptor; G_olf; G_s; striatum; knockout

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERALS AND METHODS RESULTS DISCUSSION REFERENCES

The dopamine D₁ receptor is the most abundant and widespread of the five known dopamine receptor subtypes. It is highly expressed in the striatum, nucleus accumbens, and olfactory tubercle and is moderately expressed in the cortex, amygdala, hypothalamus, and thalamus (Gingrich and Caron, 1993; Jaber et al., 1996; Missale et al., 1998). The D₁ receptor is also found on the terminals of striatal neurons in the substantia nigra pars reticulata (Altar and Hauser, 1987). D₁ receptors stimulate the formation of cAMP in response to agonists both in intact preparations (Hess et al., 1987; Watts et al., 1993) and in a number of D₁-transfected cell lines (Dearry et al., 1990; Monsma et al., 1990; Zhou et al., 1990). It is thus generally assumed that the coupling of dopamine D₁ receptors to adenylyl cyclase is mediated by G_s. However, several studies have shown that the striatum, despite its high D₁ receptor level, has very little G_s subunit, whereas it does express high levels of another G-protein subunit, G_olf (Drinnan et al., 1991; Herve et al., 1995; Belluscio et al., 1998), which was found originally to mediate olfactory receptor signaling (Jones and Reed, 1989). G_olf and G_s share 88% homology in amino acid composition, both stimulate adenylyl cyclase (Jones and Reed, 1989), and both are substrates for covalent ADP-ribosylation catalyzed by cholera toxin (Jones et al., 1990). In addition, there are no specific G_olf or G_s inhibitors.

Recently, a mouse line deficient in G_olf has been generated (G_olf knockout). These mice are anosmic because of the lack of olfactory receptor signaling (Belluscio et al., 1998). They also provide the means to test the role of G_olf in D₁ signaling. We have found that G_olf knockout mice are deficient in striatal dopamine D₁ receptor-mediated behavioral and biochemical effects, consistent with the hypothesis that G_olf mediates D₁ signaling in the striatum.

	MATERALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERALS AND METHODS RESULTS DISCUSSION REFERENCES

Animals. The generation of G_olf knockout mice has been detailed previously (Belluscio et al., 1998). Wild-type and knockout littermates have a mixed (129/Sv X C57BL/6) background and were backcrossed at least three times into the C57BL/6 strain. Only male mice were used in all of the studies. All mice were kept on a 6 A.M.-6 P.M. light cycle. All animal procedures were approved by the Institutional Animal Care and Use Committee.

In situ hybridization. In situ hybridization was performed on 20 µm fresh frozen sections with ³³P-UTP-labeled riboprobes. cDNA clones encoding G_olf (Jones and Reed, 1989) and G_s (Sullivan et al., 1986) were obtained by RT-PCR. Under the in situ hybridization conditions that were used, the G_olf and G_s probes did not cross-hybridize (Belluscio et al., 1998).

Immunohistochemistry. Animals (n = 3 for both genotypes) were deeply anesthetized with ketamine and transcardially perfused with 4% paraformaldehyde. Sections (45 µm) were cut on a freezing-sliding microtome. The primary antibody was directed against the c-fos N-peptide (AB-2; Oncogene Sciences, Mineola, NY) and used at 1:500 dilution. Fos immunoreactivity was visualized with the avidin-biotin-peroxidase method (Vectostatin Elite ABC; Vector, Burlingame, CA). The peroxidase reaction was developed in diaminobenzidine and H₂O₂.

Locomotor activity. All mice (n = 5 for both genotypes) were kept on a 6 A.M.-6 P.M. light cycle. Male mice between 3 and 5 months old were used and tested during the light period. Animals were placed in square open chambers (40 cm long × 40 cm wide × 37 cm high). They were monitored throughout the test session by a video tracking system equipped with infrared beams (PolyTrack, San Diego Instruments) that records the animal's location and path (horizontal activity) as well as the number of rearings (vertical activity). Before each test, the open fields were cleaned to maintain constant olfactory cues.

Drug treatment. Drugs were dissolved in saline and administered intraperitoneally. Animals' locomotor activities were monitored right after the injection (n = 5 for each genotypes). (±)-SKF-81297 hydrobromide was obtained from RBI (Natick, MA), and cocaine was obtained from Sigma (St. Louis, MO).

Autoradiography. Coronal fresh frozen sections were cut at 20 µm and thaw-mounted onto slides. Wild-type and mutant brain (n = 4 for each genotype) sections of comparable brain regions were mounted on the same slides. For dopamine D₁ binding, sections were dried at room temperature, preincubated for 30 min in 50 mM Tris buffer containing (in mM): 120 NaCl, 5 KCl, 2 CaCl₂, 1 MgCl₂, and 0.001% ascorbic acid, pH 7.4, and then incubated for 90 min in the same buffer supplemented with 2 nM n-methyl-³H-SCH23390 (85.0 Ci/mmol; Amersham, Arlington Heights, IL) and 50 nM ketanserin (to block 5-HT2 receptor binding). Nonspecific binding was determined in the presence of 10 µM flupenthixol. For displacement studies, alternate slides were incubated with various concentrations of dopamine (1, 4, 10, 25, 50, 100, 200, 400, 800, and 1600 µM) (Altar and Marien, 1987; Richfield et al., 1989).

Data analysis. Data were analyzed using StatView 4.5 (Abacus Concepts Inc.). Unpaired two-tailed Student's t test was used when genotype was the only grouping variable. ANOVA was used when genotype was not the only grouping variable and when data were collected in a single trial of a single session. Repeated measure ANOVA was used when data were collected in multiple trials of a single session. Nested repeated measure ANOVA was used when data were collected in multiple trials in more than one session.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERALS AND METHODS RESULTS DISCUSSION REFERENCES

G_olf but not G_s is highly expressed in the striatum

The distribution of G_olf mRNA and G_s mRNA in wild-type mice was studied by in situ hybridization with G_olf and G_s RNA probes, respectively. G_olf mRNA is highly expressed in the caudate-putamen, nucleus accumbens, olfactory tubercle, piriform cortex, dentate gyrus, CA3 region of the hippocampus (Fig. 1a,c), and Purkinje cells of the cerebellum (data not shown). There are low levels of G_olf expression in the thalamus, hypothalamus, lateral septum, bed nucleus of the stria terminalis, preoptic area (Fig. 1a,c), and substantia nigra (data not shown). In contrast, G_s mRNA is widely expressed except in the caudate-putamen, nucleus accumbens, and olfactory tubercle, where it is barely detectable (Fig. 1b,d). In G_olf knockout mice, G_olf mRNA is undetectable, whereas the level of G_s is unchanged (Belluscio et al., 1998).

View larger version (84K): [in this window] [in a new window]   Figure 1.   The distribution of Golf and Gs. The distribution of Golf mRNA (a, c) and Gs mRNA (b, d) in wild-type mice was studied by in situ hybridization with Golf and Gs RNA probes, respectively. Golf mRNA is highly expressed in the CPu, NAc, OT, Pir, DG, and CA3 (a, c). There is a low level of Golf expression in the Th, HyT, LS, BST, and POA. Gs mRNA is highly expressed everywhere except in CPu, NAc, and OT, where it is barely detectable. ac, Anterior commissure; AO, anterior olfactory nuclei; BST, bed nucleus stria terminalis; CA1, CA1 field of hippocampus; CA2, CA2 field of hippocampus; CA3, CA3 field of hippocampus; cc, corpus callosum; CPu, caudate-putamen (striatum); Cx, cortex; DG, dentate gyrus; fi, fimbria hippocampus; HyT, hypothalamus; LPA, lateral preoptic area; LS, lateral septum; MCPO, magnocellular preoptic nucleus; MPA, medial preoptic area; MS, medial septum; NAc, nucleus accumbens; OT, olfactory tubercle; ox, optic chiasm; Pir, piriform cortex; POA, preoptic area; Th, thalamus; VP, ventral pallidum.

G_olf knockout mice do not display D₁ receptor-dependent locomotor responses

Because striatal D₁ receptor activation leads to behavioral stimulation, we examined the locomotor and rearing activities of G_olf knockout mice both in baseline conditions and in response to direct and indirect D₁ agonists. Both locomotor (Fig. 2a,b) and rearing activities (data not shown) of knockout mice were significantly higher in three 1 hr open field daily sessions compared with wild-type mice. Nevertheless, knockout mice showed normal within-session (Fig. 2a) and between-session habituation (Fig. 2b).

View larger version (32K): [in this window] [in a new window]   Figure 2.   Basal and drug-induced locomotor activity in the open field. Naive animals were exposed to the open field, and their horizontal activity (total path length) was monitored for 1 hr (each point represents 5 min in a and c; the average activity during the hour is shown in b and d) for 3 consecutive days. Locomotor activity of knockout mice is significantly higher than that of wild-type mice on all 3 d (a, b, F(1,8) = 26.0; p < 0.001). The D1-selective agonist SKF-81297 (8 mg/kg) and cocaine (20 mg/kg) elicited a significant increase in locomotor activity in wild-type mice, whereas they had no effect in Golf knockout mice (c, d). There is a significant genotype × treatment interaction (F(2,16) = 24.5; p < 0.0001).

As previously reported, the D₁-selective agonist SKF-81297 (8 mg/kg) evoked increases in locomotor activity (Fig. 2c,d) and rearing (data not shown) in wild-type mice. In contrast, SKF-81297 did not stimulate locomotor activity (Fig. 2c,d) or rearing in G_olf knockout mice. Similarly, cocaine (20 mg/kg) dramatically increased locomotor activity (Fig. 2c,d) and rearing (data not shown) in wild-type mice but had no effect in G_olf knockout mice (Fig. 2c,d). Cocaine also caused mild stereotypy in wild-type mice but not in knockout mice (data not shown).

G_olf knockout mice do not display cocaine-induced c-fos expression in the striatum

The expression of the immediate-early gene c-fos is markedly induced in the striatum in response to psychostimulants such as cocaine (Graybiel et al., 1990; Lucas et al., 1997). Mice were injected with 20 mg/kg body weight cocaine or saline, killed 2 hr later, and studied for c-fos expression by immunohistochemistry. In saline-injected wild-type or G_olf knockout mice, virtually no c-fos expression was detected in the brain (data not shown). In response to cocaine, wild-type but not G_olf knockout mice displayed c-fos expression in the striatum (Fig. 3). In the cingulate cortex, lateral septum (Fig. 3), and piriform cortex (data not shown), c-fos was markedly induced in both genotypes. There were also low levels of cocaine-induced c-fos expression in the thalamus, hypothalamus, parietal cortex, and perirhinal cortex in both genotypes (data not shown).

View larger version (101K): [in this window] [in a new window]   Figure 3.   Cocaine-induced c-fos expression. Mice were injected with 20 mg/kg cocaine and killed 2 hr later for immunohistochemical studies. There was a dramatic increase in c-fos immunoreactive nuclear staining in the striatum, cingulate cortex, and lateral septum in the wild-type mice in contrast to saline-injected controls. In Golf knockout mice, cocaine-induced c-fos expression was seen in the cingulate cortex and lateral septum but not in the striatum (genotype difference in the striatum: t(4) = 3.1, p = 0.035). CPu, Caudate-putamen (striatum); LS, lateral septum; V, lateral ventricle.

Decreased affinity of D₁ receptors for dopamine in the striatum of G_olf knockout mice

G-protein coupling is usually necessary for high affinity agonist binding (Adham et al., 1998; Zhao et al., 1998). To compare the state of D₁ receptor coupling in wild-type and G_olf knockout mice, we performed in vitro autoradiography on brain sections. We examined the effects of increasing concentrations of the agonist dopamine on binding of the D₁ antagonist ligand ³H-SCH23390. As shown in Figure 4, dopamine is less efficient at displacing the radioligand in the striatum of G_olf knockout mice as compared with wild-type mice. The IC₅₀ is significantly higher in G_olf knockout mice than in wild-type mice (t₍₆₎ = 2.6; p = 0.04), consistent with a decreased affinity of striatal D₁ receptors for dopamine. No genotype difference in IC₅₀ was found in the nucleus accumbens, olfactory tubercle, or substantia nigra. Specific radioligand binding was the same for both genotypes in all brain regions.

View larger version (92K): [in this window] [in a new window]   Figure 4.   Displacement of antagonist radioligand binding by agonist. In vitro autoradiography was performed on brain sections from both wild-type and Golf knockout mice. The dopamine D1 selective antagonist 3H-SCH23390 was used as the radioligand, and different concentrations of dopamine were used to displace 3H-SCH23390 binding. The displacement of the antagonist radioligand by dopamine in the striatum was less efficient in Golf knockout mice compared with wild-type mice. IC50 (concentration of dopamine required to displace one-half of the specific binding sites) is significantly higher in Golf knockout mice than in wild-type mice in the striatum (t(6) = 2.6; p = 0.04). There was no genotype difference in specific binding.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERALS AND METHODS RESULTS DISCUSSION REFERENCES

Dopamine D₁ receptors are coupled to G_olf in the striatum

The present study provides the first functional evidence that the dopamine D₁ receptor in the striatum is coupled to G_olf. Specifically, we show in three ways that striatal D₁ receptors are not functional in mice lacking G_olf. First, G_olf knockout mice do not display locomotor responses to the D₁-selective agonist SKF-81297. Second, both the locomotor and the c-fos-inducing effects of cocaine are absent in G_olf knockout mice. Although SKF-81297 directly activates D₁ receptors, cocaine increases extracellular dopamine concentration by blocking dopamine reuptake and acts therefore as an indirect D₁ agonist. It has been shown using D₁ antagonists (Cabib et al., 1991; Young et al., 1991; Ushijima et al., 1995) and D₁ receptor knockout mice (Xu et al., 1994a,b; Drago et al., 1996; Moratalla et al., 1996) that cocaine-induced locomotion and striatal c-fos expression are D₁ dependent. The lack of these responses in the G_olf knockout mice is therefore consistent with an inactivity of striatal D₁ receptors. Cocaine-induced c-fos expression in other brain regions of the G_olf knockout mice such as the cingulate cortex and the lateral septum could be attributable either to intact D₁-signaling in these structures or to D₁-independent mechanisms. The latter alternative is suggested by observations that cocaine induces c-fos expression in the cingulate cortex and lateral septum of D₁ knockout mice (Moratalla et al., 1996).

A third line of evidence suggesting that striatal D₁ receptors are inactive in G_olf knockout mice is the decrease in the affinity of these receptors for dopamine. A decrease in the affinity of a G-protein-coupled receptor for agonists is often associated with G-protein uncoupling (Adham et al., 1998; Zhao et al., 1998). In the absence of G_olf, striatal D₁ receptors may not be coupled to a G-protein. The other two regions with high levels of G_olf but not G_s, namely the nucleus accumbens and olfactory tubercle, did not show decreased affinity for dopamine, suggesting that D₁ receptors in these regions may be coupled to a different G-protein.

Although Golf knockout and wild-type mice are on a mixed genetic background (C57BL/6 X 129/Sv; see Materials and Methods), it is highly unlikely that the lack of responsiveness to cocaine and dopamine agonist of Golf knockout mice results from differences between two parental strains, for two reasons. First, the experimental animals are littermates and therefore contain similar proportions of both strains. Second, both 129/Sv and C57BL/6 parental strains are similarly responsive to cocaine and dopamine agonists (our unpublished results).

Two distinct D₁ signaling pathways

The midbrain dopamine system has three major projections: the nigrostriatal pathway, which is involved in motor function; the mesolimbic pathway, which is involved in reward; and the mesocortical pathway, which is involved in cognitive functions (Gingrich and Caron, 1993; Jaber et al., 1996; Missale et al., 1998). Although D₁ receptors are found in all three projection areas, there appears to be a clear segregation of their downstream pathways. G_olf is highly expressed in the striatum (nigrostriatal pathway), whereas G_s is barely detectable there but highly expressed in the cortex (mesocortical pathway). The mesolimbic pathway, on the other hand, has both kinds of stimulatory G-proteins, with G_olf in the nucleus accumbens and the olfactory tubercle, G_s in the septum, and both G_olf and G_s in the piriform cortex.

Segregation in adenylyl cyclase distribution has also been reported. Specifically, adenylyl cyclase type V (AC5) is found to be restricted to the striatum, nucleus accumbens, and olfactory tubercle, whereas adenylyl cyclase type I (AC1) is barely detectable in these three regions but is widely distributed in other brain regions (Mons et al., 1995; Matsuoka et al., 1997; Shishido et al., 1997). This AC1 versus AC5 segregation matches well with the G_s versus G_olf segregation. It is therefore likely that D₁ signaling in the nigrostriatal pathway is primarily mediated by D₁-G_olf-AC5 coupling, whereas D₁ signaling in the mesocortical pathway is mediated by D₁-G_s-AC1 coupling.

The distinction between these two D₁ signaling pathways is also seen within the striatum during development. The striatum expresses G_s and AC1 but not G_olf or AC5 before the first postnatal week (Rius et al., 1994; Matsuoka et al., 1997), and there is a progressive switch from D₁-G_s-AC1 to D₁-G_olf-AC5 during the first 3 postnatal weeks. It will be interesting to investigate whether these two signaling pathways have different functional properties and how such differences may impact on the development and function of the nigrostriatal pathway.

	FOOTNOTES

Received April 10, 2000; revised June 1, 2000; accepted June 2, 2000.

This work was supported in part by a Bristol-Myers Squibb Neuroscience Award (R.H.). We thank Richard Axel for providing the Golf knockout mice. We thank Suhan Kassir for help with autoradiography study and Kimberly Scearce-Levie for setting up the open field.

Correspondence should be addressed to Rene Hen, Center for Neurobiology and Behavior, Columbia University, 722 West 168th Street, PI Annex, New York, NY 10032. E-mail: rh95{at}columbia.edu.

Dr. Belluscio's present address: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710.

This article is published in The Journal of Neuroscience, Rapid Communications Section, which publishes brief, peer-reviewed papers online, not in print. Rapid Communications are posted online approximately one month earlier than they would appear if printed. They are listed in the Table of Contents of the next open issue of JNeurosci. Cite this article as: JNeurosci, 2000, 20:RC91 (1-5). The publication date is the date of posting online at www.jneurosci.org.

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERALS AND METHODS RESULTS DISCUSSION REFERENCES

• Adham N, Zgombick JM, Bard J, Branchek TA (1998) Functional characterization of the recombinant human 5-hydroxytryptamine7(a) receptor isoform coupled to adenylate cyclase stimulation. J Pharmacol Exp Ther 287:508-514.
• Altar CA, Hauser K (1987) Topography of substantia nigra innervation by D1 receptor-containing striatal neurons. Brain Res 410:1-11.
• Altar CA, Marien MR (1987) Picomolar affinity of 125I-SCH 23982 for D1 receptors in brain demonstrated with digital subtraction autoradiography. J Neurosci 7:213-222.
• Belluscio L, Gold GH, Nemes A, Axel R (1998) Mice deficient in G(olf) are anosmic. Neuron 20:69-81.
• Cabib S, Castellano C, Cestari V, Filibeck U, Puglisi-Allegra S (1991) D1 and D2 receptor antagonists differently affect cocaine-induced locomotor hyperactivity in the mouse. Psychopharmacology 105:335-339.
• Dearry A, Gingrich JA, Falardeau P, Fremeau Jr RT, Bates MD, Caron MG (1990) Molecular cloning and expression of the gene for a human D1 dopamine receptor. Nature 347:72-76.
• Drago J, Gerfen CR, Westphal H, Steiner H (1996) D1 dopamine receptor-deficient mouse: cocaine-induced regulation of immediate-early gene and substance P expression in the striatum. Neuroscience 74:813-823.
• Drinnan SL, Hope BT, Snutch TP, Vincent SR (1991) Golf in the basal ganglia. Mol Cell Neurosci 2:66-70.
• Gingrich JA, Caron MG (1993) Recent advances in the molecular biology of dopamine receptors. Annu Rev Neurosci 16:299-321.
• Graybiel AM, Moratalla R, Robertson HA (1990) Amphetamine and cocaine induce drug-specific activation of the c-fos gene in striosome-matrix compartments and limbic subdivisions of the striatum. Proc Natl Acad Sci USA 87:6912-6916.
• Herve D, Rogard M, Levi-Strauss M (1995) Molecular analysis of the multiple Golf alpha subunit mRNAs in the rat brain. Brain Res Mol Brain Res 32:125-134.
• Hess EJ, Battaglia G, Norman AB, Creese I (1987) Differential modification of striatal D1 dopamine receptors and effector moieties by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in vivo and in vitro. Mol Pharmacol 31:50-57.
• Jaber M, Robinson SW, Missale C, Caron MG (1996) Dopamine receptors and brain function. Neuropharmacology 35:1503-1519.
• Jones DT, Reed RR (1989) Golf: an olfactory neuron-specific G protein involved in odorant signal transduction. Science 244:790-795.
• Jones DT, Masters SB, Bourne HR, Reed RR (1990) Biochemical characterization of three stimulatory GTP-binding proteins. The large and small forms of Gs and the olfactory-specific G-protein, Golf. J Biol Chem 265:2671-2676.
• Lucas JJ, Segu L, Hen R (1997) 5-Hydroxytryptamine1B receptors modulate the effect of cocaine on c-fos expression: converging evidence using 5-hydroxytryptamine1B knockout mice and the 5-hydroxytryptamine1B/1D antagonist GR127935. Mol Pharmacol 51:755-763.
• Matsuoka I, Suzuki Y, Defer N, Nakanishi H, Hanoune J (1997) Differential expression of type I, II, and V adenylyl cyclase gene in the postnatal developing rat brain. J Neurochem 68:498-506.
• Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998) Dopamine receptors: from structure to function. Physiol Rev 78:189-225.
• Mons N, Harry A, Dubourg P, Premont RT, Iyengar R, Cooper DM (1995) Immunohistochemical localization of adenylyl cyclase in rat brain indicates a highly selective concentration at synapses. Proc Natl Acad Sci USA 92:8473-8477.
• Monsma Jr FJ, Mahan LC, McVittie LD, Gerfen CR, Sibley DR (1990) Molecular cloning and expression of a D1 dopamine receptor linked to adenylyl cyclase activation. Proc Natl Acad Sci USA 87:6723-6727.
• Moratalla R, Xu M, Tonegawa S, Graybiel AM (1996) Cellular responses to psychomotor stimulant and neuroleptic drugs are abnormal in mice lacking the D1 dopamine receptor. Proc Natl Acad Sci USA 93:14928-14933.
• Richfield EK, Penney JB, Young AB (1989) Anatomical and affinity state comparisons between dopamine D1 and D2 receptors in the rat central nervous system. Neuroscience 30:767-777.
• Rius RA, Mollner S, Pfeuffer T, Loh YP (1994) Developmental changes in Gs and G(olf) proteins and adenylyl cyclases in mouse brain membranes. Brain Res 643:50-58.
• Shishido T, Watanabe Y, Suzuki H, Kato K, Niwa S, Hanoune J, Matsuoka I (1997) Effects of repeated methamphetamine administration on dopamine D1 receptor, D2 receptor and adenylate cyclase type V mRNA levels in the rat striatum. Neurosci Lett 222:175-178.
• Sullivan KA, Liao YC, Alborzi A, Beiderman B, Chang FH, Masters SB, Levinson AD, Bourne HR (1986) Inhibitory and stimulatory G proteins of adenylate cyclase: cDNA and amino acid sequences of the alpha chains. Proc Natl Acad Sci USA 83:6687-6691.
• Ushijima I, Carino MA, Horita A (1995) Involvement of D1 and D2 dopamine systems in the behavioral effects of cocaine in rats. Pharmacol Biochem Behav 52:737-741.
• Watts VJ, Lawler CP, Gilmore JH, Southerland SB, Nichols DE, Mailman RB (1993) Dopamine D1 receptors: efficacy of full (dihydrexidine) vs. partial (SKF38393) agonists in primates vs. rodents. Eur J Pharmacol 242:165-172.
• Xu M, Hu XT, Cooper DC, Moratalla R, Graybiel AM, White FJ, Tonegawa S (1994a) Elimination of cocaine-induced hyperactivity and dopamine-mediated neurophysiological effects in dopamine D1 receptor mutant mice. Cell 79:945-955.
• Xu M, Moratalla R, Gold LH, Hiroi N, Koob GF, Graybiel AM, Tonegawa S (1994b) Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses. Cell 79:729-742.
• Young ST, Porrino LJ, Iadarola MJ (1991) Cocaine induces striatal c-fos-immunoreactive proteins via dopaminergic D1 receptors. Proc Natl Acad Sci USA 88:1291-1295.
• Zhao MM, Gaivin RJ, Perez DM (1998) The third extracellular loop of the beta2-adrenergic receptor can modulate receptor/G protein affinity. Mol Pharmacol 53:524-529.
• Zhou QY, Grandy DK, Thambi L, Kushner JA, Van Tol HHM, Cone R (1990) Cloning and expression of human and rat D1 dopamine receptors. Nature 347:76-79.

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/$05.00/0

This article has been cited by other articles:

				A. Plagge, G. Kelsey, and E. L Germain-Lee Physiological functions of the imprinted Gnas locus and its protein variants G{alpha}s and XL{alpha}s in human and mouse J. Endocrinol., February 1, 2008; 196(2): 193 - 214. [Abstract] [Full Text] [PDF]

				N. Wettschureck and S. Offermanns Mammalian G Proteins and Their Cell Type Specific Functions Physiol Rev, October 1, 2005; 85(4): 1159 - 1204. [Abstract] [Full Text] [PDF]

				W. F. Schwindinger, K. S. Betz, K. E. Giger, A. Sabol, S. K. Bronson, and J. D. Robishaw Loss of G Protein gamma 7 Alters Behavior and Reduces Striatal alpha olf Level and cAMP Production J. Biol. Chem., February 14, 2003; 278(8): 6575 - 6579. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhuang, X. Articles by Hen, R. Search for Related Content PubMed PubMed Citation Articles by Zhuang, X. Articles by Hen, R. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB COCAINE DOPAMINE

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help