Effects of dopamine antagonists in a two-way active avoidance procedure in rats: Interactions with 8-OH-DPAT, ritanserin, and prazosin

Using a conditioned avoidance procedure in rats, the present study examined the ability of 8-OH-DPAT, ritanserin, and prazosin to alter the effects of the dopamine antagonists, raclopride and haloperidol, on avoidance- and on escape responding. The 5-HT(1A) agonist 8-OH-DPAT (0.16 mg/kg) significantly enhanced the inhibitory effects of both raclopride and haloperidol on the conditioned avoidance response and produced a small enhancement of the effects of haloperidol on escape failures. The α₁-adrenoceptor antagonist prazosin (0.63 mg/kg) significantly enhanced the effects of raclopride on the conditioned avoidance response, but enhanced the effects of only a single dose of haloperidol; prazosin did not alter the effects of either dopamine antagonist on escape failures. The 5-HT₂ antagonist ritanserin (0.16 mg/kg) failed significantly to alter the effects of the dopamine antagonists examined here. These findings suggest that blockade of 5-HT₂ receptors may not enhance the antipsychotic efficacy of D₂-like antagonists. Further, they confirm previous findings with respect to interactions between 5-HT(1A) agonists and neuroleptics, and support the hypothesis that combined 5-HT(1A) agonist/D₂-like antagonist properties may be of clinical importance.