The reinforcing effects of ethanol within the nucleus accumbens shell involve activation of local GABA and serotonin receptors.
Ethanol is reinforcing within the nucleus accumbens shell (NACsh), but the underlying mechanisms remain unclear. Ethanol can potentiate the function of the GABAA, GABAB, and serotonin-3 (5-HT3) receptors. Therefore, the current study tested the hypothesis that activation of these receptors would be involved in the reinforcing effects of ethanol in the NACsh. An intracranial self-administration (ICSA) procedure was used to assess the reinforcing effects of ethanol in the NACsh of alcohol preferring (P) rats. The ICSA consisted of seven sessions: four sessions to establish 150 mg% ethanol self-infusion into the NACsh; sessions 5 and 6 with co-infusion of ethanol plus one concentration of the GABAA antagonist bicuculline (10 or 100 µM), the GABAB antagonist SCH 50911 (50, 75 or 100 µM), or the 5-HT3 receptor antagonist zacopride (10 or 100 µM); and session 7 with 150 mg% ethanol alone. All groups self-infused ethanol into the NACsh and readily discriminated the active from inactive lever during the acquisition sessions. Co-infusion of 100 µM, but not 10 µM, bicuculline or zacopride significantly decreased active responses during sessions 5 and 6. Co-infusion of 75 µM, but not 50 or 100 µM, SCH 50911 significantly attenuated responses for ethanol. Overall, the results suggest that the reinforcing effects of ethanol in the NACsh may be modulated by activation of local GABAA, GABAB and 5-HT3 receptors.
Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA zding@iupui.edu.
Zheng-Ming
ZM
Ding
Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
Cynthia M
CM
Ingraham
Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
Zachary A
ZA
Rodd
Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
William J
WJ
McBride
D000428:Alcohol Drinking / Q000009:adverse effects; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000379:methods; D012701:Serotonin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; C055971:zacopride; D001640:Bicuculline
GABAA receptor; GABAB receptor; Intracranial self-administration; ethanol; nucleus accumbens; serotonin receptor