Haloperidol reduces ethanol-induced motor activity stimulation but not conditioned place preference

Risinger, Fred O.; Dickinson, Shelly D.; Cunningham, Christopher L.

doi:10.1007/bf02245175

Cited by 100 publications

(53 citation statements)

References 13 publications

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“…With regard to the invovement of the D2 receptor in ethanol-CPP, the results are not clear. Ethanol (2.0g/kg)-CPP has recently been shown to be reduced in D2 receptor knockout mice (Cunningham et al, 2000) but not after the D2/D3 antagonist haloperidol treatment (Cunningham et al, 1992b;Risinger et al, 1992). Results of the present study are not consistent with previous studies that demonstrated lower ethanol intake (Phillips et al, 1998) or ethanol-CPP (Cunningham et al, 2000) in D2…”

Section: Discussionsupporting

confidence: 38%

CB1 Receptor Knockout Mice Display Reduced Ethanol-Induced Conditioned Place Preference and Increased Striatal Dopamine D2 Receptors

Houchi

Babovic

Pierrefiche

et al. 2004

Neuropsychopharmacol

174

145

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Cannabinoids and ethanol activate the same reward pathways, and recent advances in the understanding of the neurobiological basis of alcoholism suggest that the CB 1 receptor system may play a key role in the reinforcing effects of ethanol and in modulating ethanol intake. In the present study, male CB 1 receptors knockout mice generated on a CD1 background displayed decreased ethanol-induced conditioned place preference (CPP) compared to wild-type (CB 1 þ / þ ) mice. Ethanol (0.5, 1.0, 1.5, and 2.0 g/kg) induced significant CPP in CB 1 þ / þ mice at all doses tested, whereas it induced significant CPP only at the highest dose of ethanol (2.0 g/kg) in CB 1 À/À mice.However, there was no genotypic difference in cocaine (20 mg/kg)-induced CPP. There was also no genotypic difference, neither in cocaine (10-50 mg/kg) nor in D-amphetamine (1.2-5 mg/kg)-induced locomotor effects. In addition, mutant and wild-type mice did not differ in sensitivity to the anxiolytic effects of ethanol (1.5 g/kg) when tested using the elevated plus maze. Interestingly, this decrease in ethanol efficacy to induce CPP in CB 1 À/À mice was correlated with an increase in D2/D3 receptors, as determined by [ 3 H]raclopride binding, whereas there was no difference in D1-like receptors, as determined by [ 3 H]SCH23390 binding, measured in the striatum from drug-naïve mice. This increase in D2/D3 binding sites observed in CB 1 knockout mice was associated with an altered locomotor response to the D2/D3 agonist quinpirole (low doses 0.02-0.1 mg/kg) but not to an alteration of quinpirole (0.1-1.0 mg/kg)-induced CPP compared to wild-type mice. Altogether, the present results indicate that lifelong deletion of CB 1 receptors reduced ethanol-induced CPP and that these reduced rewarding effects of ethanol are correlated to an overexpression of striatal dopamine D2 receptors.

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Section: Discussionsupporting

confidence: 38%

CB1 Receptor Knockout Mice Display Reduced Ethanol-Induced Conditioned Place Preference and Increased Striatal Dopamine D2 Receptors

Houchi

Babovic

Pierrefiche

et al. 2004

Neuropsychopharmacol

174

145

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“…The discrepant findings with D 3 receptor knockout studies might be explained by changes during the development of the genetically modified animal to compensate for the absence of the D 3 receptor. In support of this suggestion are findings that haloperidol-treated animals acquire ethanol CPP normally [234] whereas DA D 2 receptor knockout mice fail to acquire the CPP response [65]. These findings demonstrate that the behavioral effects produced by a receptor antagonist are not always compatible with those produced by genetically deleting the receptor at which the antagonist acts.…”

Section: Effect Of Sb-277011-a On Ethanol Self-administration and Relmentioning

confidence: 78%

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

Heidbreder

Gardner

et al. 2005

Brain Research Reviews

305

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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“…DA receptor antagonists attenuate the locomotor-activating effects of acute ETOH, suggesting an important role of mesoaccumbal DA neurons in mediating the acute effects of ETOH (Liljequist et al, 1981;Risinger et al, 1992;Shen et al, 1995). Behavioral sensitization after repeated ETOH administration has been demonstrated in rodents (Phillips et al, 1994;Hoshaw and Lewis, 2001;Fish et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Repeated Ethanol Intoxication Induces Behavioral Sensitization in the Absence of a Sensitized Accumbens Dopamine Response in C57BL/6J and DBA/2J Mice

Zapata

Gonzales

Shippenberg

2005

Neuropsychopharmacol

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Repeated exposure to drugs of abuse results in an increased sensitivity to their behavioral effects, a phenomena referred to as behavioral sensitization. It has been suggested that the same neuroadaptations underlying behavioral sensitization contribute to the maintenance and reinstatement of addiction. Dysregulation of dopamine (DA) neurotransmission in the mesoaccumbens system is one neuroadaptation that is thought to lead to the compulsive drug-seeking that characterizes addiction. Evidence that sensitization to psychostimulants and opiates is associated with an enhancement of drug-evoked DA levels in the nucleus accumbens has also been obtained. Like other drugs of abuse, the acute administration of ethanol (ETOH) stimulates DA release in this brain region. Moreover, repeated ETOH experience results in an enhanced behavioral response to a subsequent ethanol challenge. Data regarding the influence of repeated ethanol intoxication and withdrawal upon mesoaccumbal DA neurotransmission is limited. Studies examining ETOH-evoked alterations in mesoaccumbal DA neurotransmission as a function of withdrawal duration are lacking. The present experiments quantified basal and ethanol-evoked DA levels 14 days and 24 h following the cessation of a repeated ETOH intoxication protocol, which results in sensitization to the locomotor activating effects of ethanol. Locomotor activity was assessed in parallel groups of animals. Studies were conducted in two mouse strains, C57BL/6J and DBA/2J, which differ in their behavioral responses to ETOH. The results indicate the development of transient tolerance to both ETOH-induced behavioral activation and evoked accumbens DA release at early withdrawal. Moreover, no enhanced DA response to a subsequent ETOH challenge could be demonstrated in ETOH experienced animals 2 weeks after withdrawal, in spite of the observation of clear behavioral sensitization at this time point. These results suggest that, at least in the case of ethanol, sensitization of the DA mesolimbic system may not be necessary for the development of behavioral sensitization.

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Haloperidol reduces ethanol-induced motor activity stimulation but not conditioned place preference

Cited by 100 publications

References 13 publications

CB1 Receptor Knockout Mice Display Reduced Ethanol-Induced Conditioned Place Preference and Increased Striatal Dopamine D2 Receptors

CB1 Receptor Knockout Mice Display Reduced Ethanol-Induced Conditioned Place Preference and Increased Striatal Dopamine D2 Receptors

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

Repeated Ethanol Intoxication Induces Behavioral Sensitization in the Absence of a Sensitized Accumbens Dopamine Response in C57BL/6J and DBA/2J Mice

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