Activation of serotonin-3 receptors increases dopamine release within the ventral tegmental area of Wistar and alcohol-preferring (P) rats.

Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Alcohol (Impact Factor: 2.26). 12/2006; 40(3):167-76. DOI: 10.1016/j.alcohol.2007.01.001
Source: PubMed

ABSTRACT The objectives of the present study were to (a) examine the effects of activating serotonin-3 (5-HT3) receptors on dopamine (DA) release in the anterior and posterior ventral tegmental area (VTA) of Wistar rats and (b) determine if there are differences in 5-HT3--stimulated DA release in the VTA between alcohol-preferring (P) and Wistar rats. Local perfusion with the 5-HT3 agonist 1-(m-chlorophenyl)-biguanide (CPBG) in the anterior and posterior VTA stimulated DA release in both the regions. The CPBG-stimulated increase in extracellular DA levels was significantly higher in the posterior than anterior VTA of Wistar rats. The basal extracellular DA levels were not significantly different between the anterior and posterior VTA of Wistar rats. However, the basal extracellular DA levels were significantly higher in the posterior VTA of Wistar rats than P rats. Local perfusion of CPBG into the posterior VTA stimulated somatodendritic DA release significantly more in the P than Wistar rat. Overall, the results indicate that there may be a heterogeneous distribution of functional 5-HT3 receptors within the VTA, with higher numbers in the posterior than anterior VTA, and that, compared to 5-HT3 receptors in Wistar rats, 5-HT3 receptors in the posterior VTA of P rats may be more responsive to stimulation.

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    ABSTRACT: Ethanol and nicotine are frequently co-abused. The biological basis for the high co-morbidity rate is not known. Alcohol-preferring (P) rats will self-administer EtOH or nicotine directly into the posterior ventral tegmental area (pVTA).
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    ABSTRACT: Alcohol and nicotine co-use can reciprocally promote self-administration and drug-craving/drug-seeking behaviors. To date, the neurocircuitry in which nicotine influences ethanol (EtOH) seeking has not been elucidated. Clinical and preclinical research has suggested that the activation of the mesolimbic dopamine system is involved in the promotion of drug seeking. Alcohol, nicotine, and serotonin-3 (5-HT3) receptors interact within the posterior ventral tegmental area (pVTA) to regulate drug reward. Recently, our laboratory has reported that systemic administration of nicotine can promote context-induced EtOH seeking. The goals of the current study were to (1) determine if microinjections of pharmacologically relevant levels of nicotine into the pVTA would enhance EtOH seeking, (2) determine if coadministration of nicotinic cholinergic receptor antagonist (nACh) or 5-HT3 receptor antagonists would block the ability of nicotine microinjected into the pVTA to promote EtOH seeking, and (3) determine if 5-HT3 receptors in the pVTA can modulate EtOH seeking. Nicotine (100 and 200 μM) microinjected into the pVTA enhanced EtOH seeking. Coinfusion with 200 μM mecamylamine (nACh antagonist) or 100 and 200 μM zacopride (5-HT3 receptor antagonist) blocked the observed nicotine enhancement of EtOH seeking. The data also indicated that microinjection of 1 μM CPBG (5-HT3 receptor agonist) promotes context-induced EtOH seeking; conversely, microinjection of 100 and 200 μM zacopride alone reduced context-induced EtOH seeking. Overall, the results show that nicotine-enhanced EtOH-seeking behavior is modulated by 5-HT3 and nACh receptors within the pVTA and that the 5-HT3 receptor system within pVTA may be a potential pharmacological target to inhibit EtOH-seeking behaviors.
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