Effects of D1 dopamine receptor agonists on oral ethanol self-administration in rats: comparison with their efficacy to produce grooming and hyperactivity.
In order to study the potential efficacy of dopamine receptor agonists in the treatment of alcohol abuse, the present study investigated the effects of several dopamine D1 receptor agonists with different intrinsic activities on ethanol self-administration in rats. In a separate experiment, the effects of two of the same compounds on saccharin self-administration were also studied. To investigate further the relationship between activity in reducing ethanol self-administration and efficacies to stimulate D1 receptors, the potencies of the agonists to reduce ethanol self-administration were compared with their potencies to produce hyperactivity and grooming, behaviors which are believed to involve stimulation of D1 receptors. Rats were trained to self-administer ethanol (10% v/v) orally in a free-choice two-lever operant task using a saccharin-fading procedure. Another group of rats was trained to self-administer a solution of saccharin (0.01% w/v) in a similar operant task. Pretreatment with full (R-6Br-APB, SKF 82958 and SKF 81297) and partial (SKF 38393 and SKF 77434) dopamine D1 receptor agonists dose-dependently decreased responding for ethanol. SKF 82958 and SKF 38393 also decreased responding for saccharin. Comparison of potencies to decrease ethanol self-administration with potencies to produce locomotor activity and grooming revealed that reduction of ethanol self-administration by D1 full agonists occurs at doses similar to those which produce grooming and locomotor activity. However, the partial agonists (and in particular, SKF 38393) reduced responding for ethanol at doses lower than those producing hyperactivity. The present results underline the involvement of D1 dopamine receptors in reward processes.
Cohen
C
C
Synthelabo Recherche, Bagneux, France.
Perrault
G
G
Sanger
D J
DJ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000284:Administration, Oral; D000428:Alcohol Drinking / Q000188:drug therapy*; D000437:Alcoholism / Q000188:drug therapy; D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000431:Ethanol / Q000008:administration & dosage*; D006120:Grooming / Q000187:drug effects*; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D012439:Saccharin / Q000008:administration & dosage; D012646:Self Administration
D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D000431:Ethanol; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C071262:SK&F 82958; D012439:Saccharin