Do autoreceptors mediate dopamine agonist — induced yawning and suppression of exploration? A critical review

Ståhle, Lars

doi:10.1007/bf02253581

Cited by 82 publications

(29 citation statements)

References 93 publications

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“…The existence of behaviourally inhibitory postsynaptic "D 2 like" receptors has been proposed in behavioural studies before (Costall et al, 1981;Rubinstein et al, 1988, for review see Sffthle, 1992). The data presented here suggest that the D 3 receptor may be the target.…”

Section: Discussionmentioning

confidence: 79%

The dopamine D3-receptor: A postsynaptic receptor inhibitory on rat locomotor activity

Waters

Svensson

Haadsma‐Svensson

et al. 1993

J. Neural Transmission

247

133

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We report on the pharmacological effects of the 20 fold D3 vs. D2 dopamine receptor preferring compound U99194A. It is shown that U99194A increases rat locomotor activity at doses that do not increase release or utilisation of dopamine in the striatum or the nucleus accumbens significantly. The data do not support any direct agonist action of U99194A at dopamine receptors. It is suggested that U99194A can antagonise a population of postsynaptic dopamine receptors involved in the suppression of some aspects of psychomotor activity. These postsynaptic receptors presumably belong to the D3 receptor subtype.

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Section: Discussionmentioning

confidence: 79%

The dopamine D3-receptor: A postsynaptic receptor inhibitory on rat locomotor activity

Waters

Svensson

Haadsma‐Svensson

et al. 1993

J. Neural Transmission

247

133

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“…Quinpirole, and other direct and indirect dopamine receptor agonists, decrease locomotor activity at low doses. This suppressive effect has been interpreted as the behavioral consequence of activation of a dopamine autoreceptor, which results in a decrease in dopamine synthesis and/ or release, although this hypothesis is not universally accepted [Stahle, 1992] [Accili et al, 1996]. D 3 null mutant mice developed by Xu et al [1997] showed a different phenotype, and were only transiently more active than wild-type mice, an effect not associated with anxiety state.…”

Section: Discussionmentioning

confidence: 94%

Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D2/D3 receptors

et al. 2000

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Acute sensitivity and tolerance to quinpirole (a dopamine mimetic with selectivity for D(2)/D(3) dopamine receptors) were evaluated in the C57BL/6J and DBA/2J inbred strains of mice, 24 of their BXD recombinant inbred strains, and 233 F(2) mice. Baseline locomotor activity, locomotor activity following 0.03 mg/kg quinpirole (and 0. 01 mg/kg in BXD mice), body temperature following 1 mg/kg quinpirole, and hypothermic tolerance following 2 or 3 days of quinpirole administration were evaluated. Quantitative trait locus (QTL) analysis was employed to identify genetic determinants of baseline locomotor activity and five behavioral responses to quinpirole. We examined correlated allelic variation in genetic markers of known chromosomal location with variation in each of these phenotypes. We definitively mapped a QTL on Chromosome (Chr) 9 linked to the D(2) dopamine receptor gene, Drd2, for hypothermic sensitivity to quinpirole, and identify a suggestive QTL in the same chromosomal region for tolerance to quinpirole after repeated treatments. Suggestive QTLs were also identified on Chr 19 for sensitivity and tolerance to quinpirole-induced hypothermia and for baseline locomotor activity; on Chr 15 for locomotor sensitivity to quinpirole; and on Chr 13 and 5 for baseline locomotor activity. Our results indicate that genetic differences in quinpirole sensitivity and tolerance are associated with QTLs near Drd2, and that baseline locomotor activity is associated with a suggestive QTL in proximity to the dopamine transporter gene Dat1. These data suggest that the genes influencing locomotor activity, dopamine mimetic sensitivity, and tolerance do not overlap completely.

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“…This contention is consonant with the decrease in mesolimbic DA activity in nicotine withdrawal reported in the present and previous (Hildebrand et al 1998) studies from our laboratory. Other data, however, report a lack of correlation between changes in NAC DA output and yawning behavior elicited by DA agonists, DA synthesis inhibitors, or DA storage blockers (Ståhle 1987(Ståhle , 1992. In these studies, however, the experiments were performed almost immediately following implantation of the microdialysis probe and changes in extracellular DA may well have been blunted by the acute tissue trauma (Westerink 1995).…”

Section: Discussionmentioning

confidence: 98%

Behavioral and Biochemical Manifestations of Mecamylamine-Precipitated Nicotine Withdrawal in the Rat Role of Nicotinic Receptors in the Ventral Tegmental Area

Hildebrand

Panagis

Svensson

et al. 1999

Neuropsychopharmacology

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Brain mesolimbic dopamine (DA) neurons are considered critical for the dependence-producing action of nicotine, and its stimulatory effect on behavior and DA neurotransmission appears largely mediated via nicotinic receptors (nAChRs) in the ventral tegmental area (VTA). The nAChR antagonist mecamylamine administered systemically in chronically nicotine-treated rats elicits a behavioral withdrawal syndrome concomitant with a reduced DA output in the nucleus accumbens (NAC). Here, we investigated the behavioral and biochemical consequences of intrategmental administration of mecamylamine in rats chronically infused with nicotine by means of minipumps for 14 days (9 mg/kg/day). Bilateral, intrategmental mecamylamine injections (1, 3 or 9 g/0.5 l/ side) dose-dependently increased abstinence signs such as gasps, teeth chatter, and reduced locomotor activity in nicotine-treated, but not in control animals. Moreover, a unilateral intrategmental injection of 9 g mecamylamine reduced DA output in the ipsilateralThe habit of tobacco smoking is widely considered to represent a form of drug addiction to nicotine (Clarke 1990;Corrigall et al. 1992) and, in fact, constitutes the leading preventable cause of human morbidity and premature mortality in the US (US Department of Health and Human Services 1988). Although smokers are usually aware of the negative health consequences of their habit, the prognosis of successful smoking cessation is relatively poor. Thus, approximately 80% of smokers enrolled in cessation programmes fail to quit (Stitzer and Gross 1988). A nicotine withdrawal reaction, which usually emerges within 24 hrs after the last cigarette, is considered to significantly contribute to the high relapse rate during the early stages of attempted cessation (Shiffman and Jarvik 1976;Hughes et al. 1992;Killen et al. 1991;West et al. 1989), although a lack of correlation Received December 10, 1998; revised April 7, 1999; accepted April 20, 1999. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 21 , NO . 4 Role of VTA Nicotinic Receptors in Nicotine Withdrawal 561 between withdrawal severity and probability for relapse has been reported in other studies (see Hughes et al. 1991).In rats chronically treated with nicotine, sudden withdrawal precipitated by systemic administration of the non-competitive nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (Malin et al. 1994;Hildebrand et al. 1997), as well as spontaneous withdrawal caused by termination of a chronic nicotine infusion (Malin et al. 1992;Hildebrand et al. 1997), produces behavioral symptoms similar to those described in opiate withdrawal (see Bläsig et al. 1973). Acute as well as chronic administration of nicotine increases locomotor activity in rats (Benwell and Balfour 1992;Clarke and Kumar 1983;Stolerman et al. 1973), whereas in nicotine withdrawal locomotor activity is markedly reduced (Malin et al. 1992(Malin et al. , 1994Hildebrand et al. 1997).Compelling evidence indicates that the mesolimbic dopamine (DA) system plays a pivotal role in mediati...

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Do autoreceptors mediate dopamine agonist — induced yawning and suppression of exploration? A critical review

Cited by 82 publications

References 93 publications

The dopamine D3-receptor: A postsynaptic receptor inhibitory on rat locomotor activity

The dopamine D3-receptor: A postsynaptic receptor inhibitory on rat locomotor activity

Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D2/D3 receptors

Behavioral and Biochemical Manifestations of Mecamylamine-Precipitated Nicotine Withdrawal in the Rat Role of Nicotinic Receptors in the Ventral Tegmental Area

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