THE YOHIMBINE-INDUCED ANTICONFLICT EFFECT IN THE RAT .1. INVOLVEMENT OF NORADRENERGIC, SEROTONERGIC AND ENDOZEPINERGIC(QUESTIONABLE) MECHANISMS

The alpha(2)-adrenoceptor antagonist yohimbine has in several previous studies been found to produce anticonflict effects comparable to thos e produced by the benzodiazepines (BDZ) in rat punished conflict model s. In this and a following paper we have tried to elucidate the neuroc hemical mechanisms underlying these effects in a modified Vogel's drin king conflict test. Since yohimbine previously has been demonstrated t o interfere both with noradrenaline (NA) and serotonin (5-HT) neuroche mistry, and, in addition, shows affinity for the BDZ binding site, we have focused on the putative involvement of these neuronal systems in the yohimbine-induced anticonflict effect. The alpha(2)-adrenoceptor a gonist clonidine (10 mu g/kg, i.p.) completely antagonized the anticon flict effect of yohimbine (3.0 mg/kg, i.p.), whereas the alpha(2)-adre noceptor agonist ST 587 (1.0 mg/kg, i.p.) had no effect. The anticonfl ict effect of yohimbine was totally abolished also following lesioning of NA neurons with 6-hydroxy-dopamine. A high dose of the mixed beta( 1) and beta(2) adrenoceptor antagonist propranolol (8.0 mg/kg, i.p.) c aused a partial blockade of the yohimbine-induced effect in intact ani mals, whereas the selective beta(1)-adrenoceptor antagonist metoprolol (4.0 mg/kg, i.p.) had no significant effect and the alpha(1)-adrenoce ptor antagonist prazosin instead potentiated the anticonflict action. The anticonflict effect of yohimbine was dose-dependently antagonized also by the 5-HT precursor L-5-hydroxytryptophan (25-100 mg/kg, i.p.). The BDZ receptor antagonist flumazenil (10 mg/kg, p.o.), as well as R o 15-4513 (1.0 mg/kg, p.o.), a partial inverse agonist at BDZ receptor s, partly, but significantly, counteracted the yohimbine-induced antic onflict effect, whereas low doses of both the chloride channel blocker picrotoxin and the GABA(A) antagonist bicuculline only tended to coun teract the yohimbine effect. Taken together, the results in the presen t behavioral paper indicate that the anticonflict effect of yohimbine involves both increased NA and decreased 5-HT activity, and that direc t or indirect activation of BDZ receptors may also be involved. Neuroc hemical findings related to these behavioral results are presented in a following paper.