The selective dopamine D3 receptor antagonist SB-277011-A attenuates ethanol consumption in ethanol preferring (P) and non-preferring (NP) rats.
The mesolimbic dopamine (DA) system plays an important role in mediating addiction to alcohol and other drugs of abuse. Recent evidence points toward the role of the DA D3 receptor (D3R) in drug-induced reward, drug-taking, as well as cue-, drug-, and stress-triggered relapse to drug-seeking behavior. Accordingly, the present study examined the effects of acute selective antagonism of the D3R on ethanol consumption in alcohol Preferring (P) and Non-Preferring (NP) rats. We employed the two-bottle choice paradigm to monitor ethanol consumption in these rats before and after treatment with 3, 10, and 30 mg/kg (i.p.) of the selective D3R antagonist SB-277011-A. Results indicated a significant attenuation in ethanol preference, intake and lick responses in P rats treated with 10 and 30 mg/kg SB-277011-A. A similar, though not as robust effect was observed in ethanol consumption in the NP rats when treated with 30 mg/kg SB-277011-A. Finally, the acute administration of SB-277011-A did not produce extrapyramidal side effects, as indicated by stable lick response-volume ratios and lick response time distributions. These results further support the notion that the D3R is important in mediating the addictive properties of alcohol and suggest that selective blockade of the D3R may constitute a new and useful target for prospective pharmacotherapeutic approaches to alcoholism.
Thanos
Panayotis K
PK
Behavioral Neuropharmacology Lab, Medical Department, Building 490, Brookhaven National Laboratory, Upton, NY 11973-5000, USA. thanos@bnl.gov
Katana
John M
JM
Ashby
Charles R
CR
Michaelides
Michael
M
Gardner
Eliot L
EL
Heidbreder
Christian A
CA
Volkow
Nora D
ND
D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D044005:Tetrahydroisoquinolines / Q000494:pharmacology / Q000627:therapeutic use*
D018492:Dopamine Antagonists; D009570:Nitriles; C409982:SB 277011; D044005:Tetrahydroisoquinolines; D000431:Ethanol