Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line: comparison with D2 receptor

Sokoloff, Pierre; Andrieux, M; Besançon, Roger; Pilon, C.; Martres, Marie‐Pascale; Giros, Bruno; Schwartz, Jean‐Charles

doi:10.1016/0922-4106(92)90107-7

Cited by 379 publications

(187 citation statements)

References 22 publications

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“…The autoreceptor in the dopaminergic forebrain is of the D2 family and it is reported that both terminal D2 and D3 autoreceptors may regulate striatal and limbic dopamine release (Patel and Kruk, 1996). Metoclopramide has similar affinity for D2 and D3 dopamine receptors (Sokoloff et al, 1992) and thus it is not possible to ascribe the autoinhibition observed here to a single subtype. Although metoclopramide also blocks 5-HT 3 receptors, we are confident that the effects observed here are mediated through D2 family dopamine receptors for two reasons.…”

Section: Discussionmentioning

confidence: 76%

Time window of autoreceptor‐mediated inhibition of limbic and striatal dopamine release

Phillips

Hancock

Stamford

2002

Synapse

117

101

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Forebrain dopamine release is under the local control of D2 family (D2 and D3) autoreceptors. In this study, autoreceptor-mediated modulation of forebrain dopamine release was investigated using amperometry in brain slices following local electrical stimulation. 350 m-thick slices of nucleus accumbens or dorsolateral neostriatum were prepared from male Wistar rats (150 -200 g) and superfused with artificial cerebrospinal fluid at 32°C. Dopamine release was evoked by electrical pulses (0.1 ms, 10 mA) across bipolar tungsten stimulating electrodes and measured at carbon fibre microelectrodes using fixed potential amperometry (ϩ300 mV vs. Ag/AgCl). Peak dopamine release on stimulation (single pulse) was 0.75 M (neostriatum) and 1.37 M (nucleus accumbens). Metoclopramide (1 M) had no significant effect on DA efflux from a single pulse in either region. Using paired pulse stimuli, dopamine release on the second pulse varied according to the interval between the two pulses. At very long intervals (Ͼ20 sec), dopamine release was similar to that for the first pulse. At shorter intervals, dopamine efflux was attenuated. Metoclopramide had no effect on second pulse dopamine release when the pulse was applied at short (Ͻ0.1 sec) or long (Ͼ5.0 sec) intervals after the first. At intermediate intervals, metoclopramide significantly increased second pulse dopamine release. The peak dopamine autoreceptor effect occurred at ϳ550 ms in neostriatum and ϳ700 ms in nucleus accumbens. The onset time is due both to diffusion of dopamine from the release sites to the autoreceptors and receptoreffector mechanisms. These findings may have implications for the local control of forebrain dopamine function in physiological and pathological states. Synapse 44: 15-22, 2002.

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Section: Discussionmentioning

confidence: 76%

Time window of autoreceptor‐mediated inhibition of limbic and striatal dopamine release

Phillips

Hancock

Stamford

2002

Synapse

117

101

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“…A number of compounds were originally reported to be selective D 3 receptor antagonists, including (+)-AJ-76 [273,274], (+)-UH-232 [273,274], U99194A [122], nafadotride [248], GR103691 [206], and DS-121 [153]. However, evidence from a variety of studies indicates that these compounds either lack sufficient in vitro and/or in vivo selectivity or interact with other receptors and therefore cannot be characterized as selective D 3 receptor antagonists (see Table 1).…”

Section: Role Of Da D 3 Receptors In Drug Addiction: Studies With Mixmentioning

confidence: 99%

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

Heidbreder

Gardner

et al. 2005

Brain Research Reviews

304

249

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The cDNA for the dopamine D 3 receptor was isolated and characterized in 1990. Subsequent studies have indicated that D 3 receptors, as well as D 3 receptor mRNA, are primarily localized in limbic regions in mammals. This finding led to the postulate that D 3 receptors may be involved in drug dependence and addiction. However, this hypothesis has been difficult to test due to the lack of compounds with high selectivity for central D 3 receptors. The interpretation of results from studies using mixed D 2 /D 3 agonists and/or antagonists is problematic because these agents have low selectivity for D 3 over D 2 receptors and it is likely that their actions are primarily related to D 2 receptor antagonism and possibly interaction with other neurotransmitter receptors. Currently, with the synthesis and characterization of new highly selective D 3 receptor antagonists such as SB-277011-A this difficulty has been surmounted. The purpose of the present article is to review, for the first time, the effects of various putative D 3 receptor selective compounds in animal models of drug dependence and addiction. The results obtained with highly selective D 3 receptor antagonists such as SB-277011-A, SB-414796, and NGB-2904 indicate that central D 3 receptors may play an important role in drug-induced reward, drug-taking, and cue-, drug-, and stressinduced reinstatement of drug-seeking behavior. Provided these results can be extrapolated to human drug addicts, they suggest that selective DA D 3 receptor antagonists may prove effective as potential pharmacotherapeutic agents to manage drug dependence and addiction.

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“…Although the mechanism(s) underlying this group difference is unclear, we speculate that because the midbrain has a high concentration of D3 receptors (65), which are more sensitive to endogenous DA than D2 receptors (66), it could reflect up-regulation of D3 receptors in marijuana abusers. Indeed, in rodents, chronic Δ (9)-tetrahydrocannabinol (THC; the main psychoactive ingredient of marijuana) increased D3 receptors in midbrain (30).…”

Section: Mp-induced Changes In DVmentioning

confidence: 99%

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

Volkow

Wang

Telang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

189

147

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Moves to legalize marijuana highlight the urgency to investigate effects of chronic marijuana in the human brain. Here, we challenged 48 participants (24 controls and 24 marijuana abusers) with methylphenidate (MP), a drug that elevates extracellular dopamine (DA) as a surrogate for probing the reactivity of the brain to DA stimulation. We compared the subjective, cardiovascular, and brain DA responses (measured with PET and [ 11 C]raclopride) to MP between controls and marijuana abusers. Although baseline (placebo) measures of striatal DA D2 receptor availability did not differ between groups, the marijuana abusers showed markedly blunted responses when challenged with MP. Specifically, compared with controls, marijuana abusers had significantly attenuated behavioral ("self-reports" for high, drug effects, anxiety, and restlessness), cardiovascular (pulse rate and diastolic blood pressure), and brain DA [reduced decreases in distribution volumes (DVs) of [ 11 C]raclopride, although normal reductions in striatal nondisplaceable binding potential (BP ND )] responses to MP. In ventral striatum (key brain reward region), MP-induced reductions in DVs and BP ND (reflecting DA increases) were inversely correlated with scores of negative emotionality, which were significantly higher for marijuana abusers than controls. In marijuana abusers, DA responses in ventral striatum were also inversely correlated with addiction severity and craving. The attenuated responses to MP, including reduced decreases in striatal DVs, are consistent with decreased brain reactivity to the DA stimulation in marijuana abusers that might contribute to their negative emotionality (increased stress reactivity and irritability) and addictive behaviors.nucleus accumbens | amotivation | cannabinoid 1 receptors | brain imaging | midbrain D espite the high prevalence of marijuana consumption, the effects of marijuana abuse in the human brain are not well understood. Marijuana, like other drugs of abuse, stimulates brain dopamine (DA) signaling in the nucleus accumbens (1, 2), which is a mechanism believed to underlie the rewarding effects of drugs (3-5) and to trigger the neuroadaptations that result in addiction (reviewed in ref. 6). Indeed, in humans, imaging studies have shown that drugs of abuse increase DA release in striatum (including the nucleus accumbens), and these increases have been associated with the subjective experience of reward (7-9). However, for marijuana, the results have been inconsistent: One study reported striatal DA increases during intoxication (10); two studies showed no effects (11, 12); and one study reported DA increases in individuals with a psychotic disorder and in their relatives, but not in controls (13). Imaging studies of the brain DA system in marijuana abusers have also shown different findings from those reported for other types of substance abusers. Specifically, substance abusers (cocaine, methamphetamine, alcohol, heroin, and nicotine), but not marijuana abusers (14-16), show reduced baseline availability ...

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Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line: comparison with D2 receptor

Cited by 379 publications

References 22 publications

Time window of autoreceptor‐mediated inhibition of limbic and striatal dopamine release

Time window of autoreceptor‐mediated inhibition of limbic and striatal dopamine release

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

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