Disinhibitory effects of buspirone and low doses of sulpiride and haloperidol in two experimental anxiety models in rats: possible role of dopamine.
Low doses of buspirone, haloperidol and sulpiride were compared with diazepam in two experimental models of anxiety in rats. In a conflict test, 0.6 and 1.2 mg/kg buspirone, 0.05 and 0.10 mg/kg haloperidol and 0.5 mg/kg sulpiride significantly increased punished responding. Buspirone 1.2 and 2.5 mg/kg significantly reduced the number of unpunished responses while haloperidol and sulpiride at the doses tested had no effect. Effects on punished responding were seen in a narrow dose range and were less pronounced with these drugs than with diazepam. Similar results were obtained with rats', activity in the two-compartment exploratory test. At doses causing no change in the locomotion of rats in photocell activity cages, buspirone (0.1 mg/kg), haloperidol (0.025-0.100 mg/kg) and sulpiride (0.5-1.0 mg/kg) significantly increased the number of crossings between the two compartments. Again, the peak effects were small when compared with the effect of diazepam and the active dose range was very narrow. Apomorphine 0.2 mg/kg SC significantly counteracted the effect of 0.1 mg buspirone and 1.0 mg/kg sulpiride in the two-compartment exploratory test with no effect on 2.5 mg/kg diazepam. The data show that buspirone, in a narrow dose range, shows disinhibitory effects in experimental models of anxiety. Similar effects are shown by low doses of haloperidol and sulpiride. It is suggested that buspirone and sulpiride produce these disinhibitory effects by blocking particular dopamine receptors in the brain, possibly those located in the nerve terminals, but it is likely that other mechanisms, particularly serotonin, are involved in the effects of buspirone in anxious states.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects*; D002065:Buspirone; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D011954:Receptors, Dopamine; D013469:Sulpiride; D006220:Haloperidol; D001058:Apomorphine; D002065:Buspirone