Regulation of methionine-enkephalin precursor messenger RNA in rat striatum by haloperidol and lithium

doi:10.1016/0006-291X(83)91739-4

Biochemical and Biophysical Research Communications

Volume 113, Issue 2, 15 June 1983, Pages 391-399

https://doi.org/10.1016/0006-291X(83)91739-4 Get rights and content

Abstract

Daily injections of rats with haloperidol for 21 days or lithium chloride for 5 days elevated the content of Met-enkephalin in the striatum by 86% or 66%, respectively. Poly(A) + RNA from striata of drug-treated and control rats was translated $in vitro$ , and the amount of synthesized enkephalin precursor [³⁵S]preproenkephalin A was determined by immunoprecipitation and SDS-polyacrylamide gel electrophoresis. Haloperidol or lithium treatment increased the relative amount of preproenkephalin A synthesized by 67–98% or 25–29%, respectively. These results suggest that haloperidol elevates the Met-enkephalin content primarily by increasing the precursor mRNA content or activity, while lithium exerts its effect only in part by this mechanism.

References (17)

J.S. Hong et al.
Neuropharmacology
(1977)
T. Hökfelt et al.
Neurosci. Lett
(1977)
J.S. Hong et al.
Brain Res
(1979)
S.L. Sabol et al.
J. Biol. Chem
(1983)
S. Dandekar et al.
Biochem. Biophys. Res. Comm
(1982)
Hughes, J., Smith, T.W., Kosterlitz, H.W., Fothergill, L.A., Morgan, B.A., and Morris, H.R. (1975) 258,...
J.S. Hong et al.
J. Pharmacol. Exp. Therap
(1978)
J.S. Hong et al.
Adv. Biochem. Psychopharmacol
(1980)

There are more references available in the full text version of this article.

Cited by (98)

Naloxone's suppression of spontaneous and food-conditioned locomotor activity is diminished in mice lacking either the dopamine D<inf>2</inf> receptor or enkephalin
2005, Molecular Brain Research
Mice lacking the D₂ dopamine receptor (D₂^−/−) and congenic to the C57BL/6J background were tested for opioid-mediated locomotor activity to examine the involvement of the D₂ dopamine receptor in opioid pharmacology. Morphine-stimulated locomotor activity did not significantly differ between the two genotypes. The opioid antagonist naloxone dose-dependently decreased spontaneous motor activity in wild-type mice but was without significant effect in D₂^−/− mice. The magnitude of food-conditioned increases in locomotor activity in wild-type mice and D₂^−/− mice was similar but naloxone did not decrease conditioned motor activity in D₂^−/− mice. Spontaneous locomotor activity of mice lacking the endogenous opioids β-endorphin and/or enkephalin was also tested and we found that naloxone did not reduce activity in mice specifically lacking enkephalin. We suggest that the D₂ dopamine receptor is necessary for modulation of spontaneous locomotor activity stimulated by the endogenous opioid enkephalin.
Facilitation of enkephalins-induced delta-opioid behavioral responses by chronic amisulpride treatment
2005, Neuroscience
The endogenous opioid system is known to have a great influence on the dopaminergic system. Conversely, blockade of the dopaminergic system in D2 receptor knock-out mice triggers an increase in enkephalin supporting the important physiological relationship between both systems. Therefore, the aim of this study was to investigate whether or not chronic treatment with the specific D2 antagonist amisulpride (20mg/kg, i.p., twice daily for 5 days) could lead to a facilitation of behavioral effects of enkephalins, protected from their enzymatic degradation by the dual inhibitor N-[(R,S)-2-benzyl-3[(S)(2-amino-4-methylthio)butyl dithio]-1-oxopropyl]-l-phenylalanine benzyl ester (RB101) (5mg/kg, i.v.) in mice.
RB101 induced an increase in locomotor activity, antidepressant-like effects in the forced swim test, and antinociceptive effects in the hot-plate test.
Chronic treatment with amisulpride potentiated the action of RB101 and this effect seemed to be restricted to behavioral responses induced by opioids acting on delta-opioid receptors (locomotor activity and forced swim test). This was confirmed by the use of the selective delta-opioid receptor agonist, (+)-4-[α-R*)-α-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80; 2.5mg/kg, i.p.), and antagonist, naltrindole (5mg/kg, i.p.).
Considering the involvement of delta-opioid receptors in mood regulation, the interaction between amisulpride and RB101 could lead to a new therapeutic approach in the treatment of some mood disorders.
Opiate-like effects of sugar on gene expression in reward areas of the rat brain
2004, Molecular Brain Research
Drugs abused by humans are thought to activate areas in the ventral striatum of the brain that engage the organism in important adaptive behaviors, such as eating. In support of this, we report here that striatal regions of sugar-dependent rats show alterations in dopamine and opioid mRNA levels similar to morphine-dependent rats. Specifically, after a chronic schedule of intermittent bingeing on a sucrose solution, mRNA levels for the D2 dopamine receptor, and the preproenkephalin and preprotachykinin genes were decreased in dopamine-receptive regions of the forebrain, while D3 dopamine receptor mRNA was increased. While morphine affects gene expression across the entire dopamine-receptive striatum, significant differences were detected in the effects of sugar on the nucleus accumbens and adjacent caudate-putamen. The effects of sugar on mRNA levels were of greater magnitude in the nucleus accumbens than in the caudate-putamen. These areas also showed clear differences in the interactions among the genes, especially between D3R and the other genes. This was revealed by a novel multivariate analysis method that identified cooperative interactions among genes, specifically in the nucleus accumbens but not the caudate-putamen. Finally, a role for these cooperative interactions in a load-sharing response to perturbations caused by sugar was supported by the finding of a different pattern of correlations between the genes in the two striatal regions. These findings support a major role for the nucleus accumbens in mediating the effects of naturally rewarding substances and extend an animal model for studying the common substrates of drug addiction and eating disorders.
Inhibition of morphine analgesia by lithium: Role of peripheral and central opioid receptors
2004, Behavioural Brain Research
Intraperitoneal (i.p.) administration of lithium chloride (LiCl) has two effects on pain sensation: (1) it induces a transient hyperalgesia that is reversed by intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of the opioid receptor antagonist naloxone or by peripheral administration of the quaternary compound naloxone methiodide [Behav. Neurosci. 114 (2000) 1183]; (2) it produces a long-lasting (24 h) reduction in morphine analgesia and does so in the absence of hyperalgesia [Behav. Brain Res. 142 (2003) 89]. We confirmed that rats administered with LiCl showed a reduction in analgesia when administered morphine 24 h later. We also found that morphine analgesia was restored if LiCl had been preceded by i.p. or i.c.v. administration of naloxone or by i.p. administration of naloxone methiodide. However, i.p. administration of naloxone methiodide prior to testing 24 h after an injection with LiCl did not restore morphine analgesia. Thus, activity at peripheral and central opioid receptors is necessary for the inhibition of morphine analgesia by LiCl, but peripheral opioid receptors are not critical for the expression of this inhibition.
Dopaminergic system modulation of nociceptive response in long-term diabetic rats
2002, Pharmacology Biochemistry and Behavior
The present study examines the effects of dopaminergic system modulation on nociceptive response time in male diabetic rats. In this study, diabetes was induced by streptozotocin (STZ, 45 mg/kg) in adult male Sprague–Dawley rats. Insulin replacement therapy was initiated 6 weeks after the induction of diabetes for one-half of the diabetic group (1.5–2.5 IU/12 h/rat) and was continued throughout the duration of the study (up to 14 weeks). After 6 weeks of daily insulin replacement therapy, eight rats from each experimental group (STZ-diabetic, STZ-diabetic+insulin and nondiabetic control) were injected with either bromocriptine (BROM, 3 mg/kg/12 h), haloperidol (HALO, 1.5 mg/kg/12 h) or vehicle. Nociceptive response was measured by the hot plate (HP) latency test before the induction of diabetes (baseline), every 3 weeks for the first 12 weeks and then on days 5, 9 and 14 of treatment with dopaminergic agents. Animals were sacrificed 3 or 4 days after the last HP test and the brain, blood, spinal cord (SC), pituitary and adrenal glands (AD) were dissected for Met-enkephalin (ME) assay. The results show that nociceptive response of untreated diabetic animals increased gradually and significantly over the duration of this study. Administration of BROM and HALO significantly decreased and increased the nociceptive response, respectively, in all groups. However, the response of the diabetic group was more pronounced than that of the other two groups, especially for those treated with BROM. Daily insulin administration normalized nociceptive response to that of the nondiabetic controls. Diabetic animals receiving insulin replacement+BROM also showed normalized nociceptive response while the diabetic animals+HALO did not. Moreover, the administration of HALO and BROM resulted in an increase and decrease ME concentrations, respectively, in most tissues and brain regions examined. The effect of these dopaminergic agents on ME levels was greater in brain regions and tissues of the diabetic rats than in the diabetic groups receiving vehicle or in the nondiabetic control receiving these two agents. These data suggest that diabetes alters the sensitivity of the dopaminergic receptors and that altered response of the dopaminergic system could be indirectly involved in the modulation of nociception in diabetic rats possibly through the enhancement and/or deactivation of the endogenous Met-enkephalinergic system.
The effect of aging on the response of striatal preproenkephalin and preprotachykinin mRNA contents to chronic haloperidol treatment in rats: Measurement by solution-hybridization RNase protection assay
1998, Neuroscience Letters
The preproenkephalin (PPeK) and preprotachykinin (PPT) mRNA contents in 3-, 10- and 23-month-old rats in the striatum were measured by solution hybridization-RNase protection assay after 3 weeks of haloperidol injection. Haloperidol increased striatal PPek mRNA. There was no age-related difference in the response of striatal PPeK mRNA to chronic haloperidol treatment. The PPT mRNA decreased by 21% after the haloperidol treatment in young rats only. Meanwhile, age decreased the PPT mRNA by 27 and 24% in 10- and 23-month-old rats, respectively. It is concluded that there is a difference in the effects of aging on the response of PPek and PPT mRNA contents to haloperidol and that the loss of PPT mRNA response in 10- and 23-month-old rats might be due to the change of dopamine system of the striatum in these rats.

View all citing articles on Scopus

View full text

Regulation of methionine-enkephalin precursor messenger RNA in rat striatum by haloperidol and lithium

Abstract

Neuropharmacology

Neurosci. Lett

Brain Res

J. Biol. Chem

Biochem. Biophys. Res. Comm

J. Pharmacol. Exp. Therap

Adv. Biochem. Psychopharmacol