INVOLVEMENT OF DOPAMINE D-2 RECEPTORS IN THE SUPPRESSIVE EFFECT OF THE THYROTROPIN-RELEASING-HORMONE ANALOG TA-0910 ON ALCOHOL INTAKE IN ALCOHOL-PREFERRING RATS

Pharmacological experiments were conducted to determine the neuronal m echanisms involved in the suppressive effects of the thyrotropin-relea sing hormone analog TA-0910 on alcohol intake in alcohol-preferring (P ) rats. We previously reported that single intraperitoneal injections of TA-0910 dose-dependently reduced alcohol intake in P rats without a ltering fluid or total calorie intake; however, after several consecut ive, once-daily injections, P rats developed tolerance to the suppress ive effects of TA-0910 on alcohol intake and cross-tolerance to like e ffects of the dopamine D-2 agonist bromocriptine, but not to like effe cts of the serotonin uptake inhibitor fluoxetine. In the present study , rats were injected with vehicle or different doses of the D-2 antago nist s (-)-eticlopride (0.01 to 0.05 mg/kg) or the D-1 antagonist R(+) -SCH23390 (0.1 to 0.5 mg/kg) and 20 min later with TA-0910 (0.75 mg/kg ), Alcohol and water intakes were measured at 2, 4, 6, and 24 hr, and food was measured every 24 hr, Both s(-)-eticlopride and R(+)-SCH23390 produced modest reductions in alcohol intake alone; however, only s(- )-eticlopride antagonized the suppressive effect of TA-0910 on alcohol intake, In related experiments, it was confirmed that the dopamine D- 3 agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin reduced alcohol in take in P rats, and it was found that tolerance to this effect did not develop during or after seven consecutive once-daily injections. Furt hermore, this effect of 7-hydroxy-N,N-di-n-propyl-2-aminotetralin was not diminished in rats made tolerant to the effect of TA-0910 on alcoh ol intake, These data, those of previous studies, and recent prelimina ry findings support involvement of dopamine D-2, but not D-1, or D-3 r eceptors in mediating the suppressive effect of TA-0910 on alcohol int ake of P rats.