Further evidence for the involvement of D2, but not D1 dopamine receptors in dopaminergic control of striatal cholinergic transmission

doi:10.1016/0024-3205(82)90679-8

Life Sciences

Volume 31, Issue 25, 20 December 1982, Pages 2883-2890

https://doi.org/10.1016/0024-3205(82)90679-8 Get rights and content

Abstract

The relative involvement of D₁ (cyclase linked) and D₂ dopamine receptors in dopaminergic control of striatal cholinergic transmission has been investigated in the rat by comparing the effects of SKF 38393 and LY 141865 (which act as specific agonists at D₁ and D₂ dopamine receptors, respectively) on striatal acetylcholine and dopamine metabolite concentrations and on the potassium-evoked release of ³H-acetylcholine from rat striatal slices. LY 141865 given systemically produced a dose-dependent increase in acetylcholine concentrations and a concomitant reduction of homovanillic and dihydroxyphenylacetic acid levels in the striatum (ED₅₀ 0.1 mg/kg) whereas SKF 38393 (1–30 mg/kg) did not. SKF 38393 (30 mg/kg) also failed to modify the LY 141865 (1 mg/kg) induced alterations of striatal acetylcholine and dopamine metabolite levels when given concomitantly with the latter compound. In experiments $in vitro$ , LY 141865 reduced (EC₅₀ 0.14 μM), whereas SKF 38393 (up to 100 μM) failed to affect, the potassium-evoked release of ³H-acetylcholine from striatal slices. When given concomitantly with LY 141865, SKF 38393 (10 μM) did not modify the ability of the former compound to diminish striatal ³H-acetylcholine release. Finally, SKF 38393 also failed to affect the release of striatal ³H-acetylcholine after chemical lesion of the nigro-striatal dopaminergic pathway. The present results provide evidence for the involvement of D₂ but not D₁ dopamine receptors in dopaminergic control of striatal cholinergic transmission and indicate that D₁ dopamine receptors do not exert any modulatory influence on D₂ dopamine receptor mediated dopaminergic transmission.

References (26)

P.E. Setler et al.
Europ. J. Pharmacol.
(1978)
P.G. Guyenet et al.
Brain Res.
(1975)
L. Semerdjian-Rouquier et al.
J. Chromatog.
(1981)
J.M. Rabey et al.
Brain Res.
(1981)
C.J. Pycock
Neuroscience
(1980)
S.R. Nahorski et al.
Neuropharmacology
(1975)
P.F. Spano et al.
P.F. Spano et al.
J.W. Kebabian et al.
Nature
(1979)
P. Seeman
Pharmacol. Rev.
(1981)

K.G. Lloyd

B. Scatton

J. Pharmacol. Exp. Ther.

(1982)

K. Tsuruta et al.

Nature

(1981)

Cited by (129)

Modulation of acetylcholine release by cholecystokinin in striatum - receptor specificity; role of dopaminergic neuronal activity
2012, Brain Research Bulletin
Citation Excerpt :
On the other hand the effect of CCK-8 on electrically induced ACh was markedly increased when the nigro-striatal dopaminergic pathway was destroyed by 6-OHDA or when D2 dopamine receptors were inhibited by sulpiride. It is well known that dopamine released from nigrostriatal axon terminals tonically inhibits the release of striatal acetylcholine via stimulation of D2 receptors (Vizi et al., 1977; Scatton, 1982; Stoof et al., 1982; Mackenzie et al., 1989; Vizi and Labos, 1991; Robertson et al., 1993). In agreement with the above hypothesis our experiments demonstrate that CCK-8 exerts a stimulatory effect on electrically evoked ACh release, an effect which is fully exposed (uncovered) whenever the inhibitory effect of endogenous dopamine is lifted.
Cholecystokinin, a neuroactive peptide functioning as a neurotransmitter and neuromodulator in the central nervous system, mediates a number of processes and is implicated in neurological and psychiatric disorders such as Parkinson's disease, anxiety and schizophrenia. Striatum is one of the brain structures with the highest concentrations of CCK in the brain, rich in CCK receptors as well. The physiological effect of CCK on cholinergic interneurons, which are the major interneurons in striatum and the modulatory interactions which exist between dopamine, acetylcholine and cholecystokinin in this brain structure are still unclear. We studied the effect of cholecystokinin octapeptide (CCK-8) on the release of acetylcholine (ACh) from striatal slices of the rat brain. CCK-8 (0.01–0.1 μM) showed no statistically significant effect on the basal but enhanced dose-dependently the electrically (2 Hz)-evoked release of [³H]ACh. When slices were preperfused with 100 μM sulpiride, a selective dopamine D₂ receptor antagonist, the CCK-8 (0.01 μM) effect on electrically stimulated ACh release was increased nearly 2-fold. A similar increase was observed after depletion of endogenous dopamine (DA) from nigro-striatal dopaminergic neurons with 6-hydroxydopamine (6-OHDA) (2× 250 μg/animal, i.c.v.). Furthermore in the presence of dopamine (100 μM) or apomorphine (10 μM), the prototypical DA receptor agonist, CCK-8 (0.01 μM) failed to enhance the stimulation-evoked release of [³H]ACh. The D₂ receptor agonist quinpirol (1 μM) abolished the CCK-8 effect on electrically stimulated ACh release as well. The increase in electrically induced [³H]ACh release produced by 0.01 μM CCK-8 was antagonized by d,l loxiglumide (CR 1505), 10 μM, a non-peptide CCK-A receptor antagonist and by Suc-Tyr-(OSO3)-Met-Gly-Trp-Met-Asp-β-phenethyl-amide (GE-410), 1 μM, a peptide CCK-A receptor antagonist. The antagonistic effect of GE-410 on the CCK-8-potentiated, electrically induced release of [³H]ACh was studied in striatum for the first time. CAM 1028 (10 μM), a CCK-B receptor antagonist, also prevented the potentiating effect of CCK-8 (0.01 μM) on electrically stimulated release of [³H]ACh.
The presented results indicate that (i) CCK-8 is capable of increasing ACh elicited by field electrical stimulation in striatum; (ii) CCK-8 is more effective in its ACh-stimulating effect when dopaminergic activity in striatum is blocked i.e. CCK-8-facilitated release of electrically induced ACh from cholinergic interneurons in the striatum is under the inhibitory control of the tonic activity of dopamine from the nigrostriatal pathway; (iii) the enhancing effect of CCK-8 on electrically evoked ACh release is mediated through both CCK-A and CCK-B cholecystokinin receptors located most likely on the cell bodies of cholinergic interneurons in striatum.
Glycine stimulates the release of labeled acetylcholine but not dopamine nor glutamate from superfused rat striatal tissue
2007, Brain Research
Citation Excerpt :
Functional studies have revealed strychnine-sensitive glycine receptors in medium size spiny neurons (GABAergic) as well as in giant aspiny neurons (cholinergic) in striatum (Darstein et al., 2000; Sergeeva, 1998; Sergeeva and Haas, 2001), suggesting a role for glycine in this nucleus. Haloperidol can directly influence striatal cholinergic transmission by disrupting dopaminergic inhibition of striatal cholinergic cells (Guyenet et al., 1975) and consequently increasing acetylcholine release (Scatton, 1982; Sethy and Van Woert, 1974). These effects lead to a behavioral picture involving muscle stiffness, hypokinesia, and tremors (Addonizio et al., 1987) commonly described in rats as catatonia (Kornhuber and Weller, 1994).
Glycine is known as an inhibitory neurotransmitter in the spinal cord and forebrain but its precise role in the forebrain is largely overlooked. This investigation evaluated whether glycine alters acetylcholine, glutamate or dopamine release from striatal tissue using an in vitro approach. We observed that while glycine induced a robust ³H-acetylcholine release (³H-ACh) from superfused striatal tissue, it failed at releasing ³H-glutamate or ³H-dopamine. Glycine stimulated ³H-ACh release in a dose- and calcium-dependent manner (EC₅₀ = 69 μM). Tetrodotoxin (1 μM) inhibited about 75% of the release demonstrating a predominant dendritic and cell body location of glycine receptors. The prototypical glycine receptor antagonist strychnine at 10 μM completely abolished ³H-ACh release. To further characterize the role of striatal glycine receptors in ³H-ACh release we examined glycine effects after in vivo treatment with Haloperidol-decanoate (HD). Treatment for 30 days or more with HD decreased maximal glycine-stimulated release of ³H-ACh suggesting a non-competitive inhibition. After 30 days of washout release parameters did not return to vehicle-treated levels. The glutamate agonist NMDA also stimulated acetylcholine release but showed slightly different behavior in HD-treated striatal tissue. These effects could be attributed to changes in chloride transporters expressed in the giant striatal cholinergic cell as well as glycine receptor subunit composition and finally, GABA/glycine co-release in this tissue.
μ Opioid control of the N-methyl-D-aspartate-evoked release of [ <sup>3</sup>h]-acetylcholine in the limbic territory of the rat striatum in vitro: Diurnal variations and implication of a dopamine link
2004, Neuroscience
Using an in vitro microsuperfusion procedure, the release of newly synthesized [³H]-acetylcholine (ACh), evoked by N-methyl-d-aspartate (NMDA) receptor stimulation, was investigated in striosome-enriched areas and matrix of the rat striatum. The role of μ-opioid receptors, activated by endogenously released enkephalin, on the NMDA-evoked release of ACh was studied using the selective μ-opioid receptor antagonist, β-funaltrexamine. Experiments were performed 2 (morning) or 8 (afternoon) h after light onset, in either the presence or absence (α-methyl-p-tyrosine, an inhibitor of dopamine synthesis) of dopaminergic transmission. As expected, based on the presence of μ-opioid receptors in striosomes, β-funaltrexamine (0.1 nM, 10 nM and 1 μM) enhanced the NMDA (1 mM+10 μM d-serine)-evoked release of ACh in striosome-enriched areas but not in the matrix. Interestingly, these responses were significantly more pronounced in afternoon than in morning experiments. In the presence of α-methyl-p-tyrosine, the NMDA-evoked release of ACh was increased with similar amplitude in morning and afternoon experiments. However, in this condition (without dopamine transmission), the facilitatory effects of β-funaltrexamine on the NMDA-evoked release of ACh were suppressed totally in the morning and only partially in the afternoon. The selective μ-opiate agonist, [d-Ala²,N-Me-Phe⁴,Gly⁵-ol]-enkephalin (1 μM, coapplied with NMDA), was without effect on the NMDA-evoked release of ACh but abolished both dopamine-dependent (morning) and dopamine-independent (afternoon) responses of β-funaltrexamine (10 nM and 1 μM).
Therefore, in the limbic territory of the striatum enriched in striosomes, the μ-opioid-inhibitory regulation of ACh release follows diurnal rhythms. While dopamine is required for this regulation in the morning and the afternoon, an additional dopamine-independent process is present only in the afternoon.
Muscarinic, adenosine A<inf>2</inf> and histamine H<inf>3</inf> receptor modulation of haloperidol-induced c-fos expression in the striatum and nucleus accumbens
2002, Neuroscience
It is generally believed that haloperidol exerts its motor side effects and therapeutic effects mainly by antagonizing dopamine D₂ receptors in the striatum and the nucleus accumbens, respectively. Several neurotransmitters/modulators, including glutamate, acetylcholine, adenosine and histamine, affect dopaminergic activity in these centers. We have recently shown that N-methyl-D-aspartate receptor-mediated modulation of haloperidol-induced c-fos expression differs in functionally specific regions of the striatum and the nucleus accumbens. In the present study, the entire striatum and the nucleus accumbens were comprehensively examined for the pattern of modulation of haloperidol-induced c-fos expression by adenosine A₂, histamine H₃ and muscarinic receptor antagonists.
Blockade of muscarinic and H₃ receptors resulted in a profound suppression of haloperidol-induced c-fos expression in the dorsolateral part of the striatum. In addition, the H₃ receptor antagonist suppressed the effects of haloperidol in the ventrolateral aspect of the striatum and the rostral parts of the medial striatum. Muscarinic receptor antagonists suppressed haloperidol-induced c-fos expression throughout the shell and in the mid-level of the core of the nucleus accumbens while A₂ and H₃ receptor antagonists did not.
We found that the muscarinic and H₃ receptor antagonists suppress the induction of c-fos by haloperidol in the dorsolateral aspect of the striatum, an area implicated in the development of extrapyramidal motor symptoms following chronic haloperidol treatment. By contrast, haloperidol-induced c-fos expression in the nucleus accumbens, an area implicated in the therapeutic effects of haloperidol, was suppressed by the muscarinic receptor antagonist, but not by the H₃ receptor antagonist. Therefore we conclude that H₃ receptor modulation may provide a useful therapeutic target in future efforts to minimize neuroleptic-induced motor side effects.
Locomotor stereotypy produced by dexbenzetimide and scopolamine is reduced by SKF 83566, not sulpiride
1998, Pharmacology Biochemistry and Behavior
Like amphetamine, scopolamine produces locomotor stereotypy (repetitive routes of locomotion) in an open field. To determine whether locomotor stereotypy is a common behavioral effect of anticholingeric agents, several doses of the anticholinergic dexbenzetimide were tested for the ability to produce locomotor stereotypy; like scopolamine, dexbenzetimide produced locomotor stereotypy. To investigate a possible role of dopamine in anticholinergic-induced locomotor stereotypy, we tested the ability of the dopamine D₁ antagonist SKF 83566 and the D₂ antagonist sulpiride to block the locomotor stereotypy induced by scopolamine as well as dexbenzetimide. SKF 83566 blocked scopolamine- and dexbenzetimide-induced locomotor stereotypy; sulpiride did not reduce dexbenzetimide-induced locomotor stereotypy, but enhanced scopolamine-induced locomotor stereotypy. Hyperlocomotion was reduced by both dopamine antagonists. Results are interpreted in support of the notion that dopamine is the likely candidate mediating locomotor stereotypy.
Lack of autoreceptor-mediated inhibitory control of dopamine release in striatal synaptosomes of D2 receptor-deficient mice
1998, Brain Research
Mouse purified striatal synaptosomes were used to study the release of newly synthesised [³H]-dopamine ([³H]-DA) or of previously taken up [³H]-DA. Quinpirole (QP, 10 μM), a D2/D3 dopaminergic agonist, was found to reduce the release of newly synthesised [³H]-DA with a larger amplitude when 4-aminopyridine (100 μM) instead than veratridine (1 μM) or potassium (25 mM) was used to evoke DA release. Among the different D2/D3 dopaminergic agonists tested R(−)-propylnorapomorphine (NPA) and quinpirole were the most potent. These compounds reduced, in a concentration-dependent manner, the 4-aminopyridine-evoked release of [³H]-DA previously taken up by synaptosomes (50% maximal inhibition). In contrast, the D3 agonist PD-128,907 had little effect even when used at 100 nM. The QP (100 nM)-induced response was completely antagonised by sulpiride (1 μM). Strikingly, the NPA (100 nM) and PD-128,907 (100 nM)-evoked responses were completely suppressed in D2 receptor-deficient mice. This data strongly suggest that only D2 but not D3 receptors are involved in the autoreceptor-mediated inhibition of the evoked release of [³H]-DA. Interestingly, while amphetamine-induced release of [³H]-DA was not modified, a slight reduction of [³H]-DA efflux induced by the dopamine (DA) uptake inhibitor cocaine was observed in D2 receptor-deficient mice.

View all citing articles on Scopus

View full text

Further evidence for the involvement of D2, but not D1 dopamine receptors in dopaminergic control of striatal cholinergic transmission

Abstract

Europ. J. Pharmacol.

Brain Res.

J. Chromatog.

Brain Res.

Neuroscience

Neuropharmacology

Nature

Pharmacol. Rev.

J. Pharmacol. Exp. Ther.

Nature

Further evidence for the involvement of D₂, but not D₁ dopamine receptors in dopaminergic control of striatal cholinergic transmission