THE ROLE OF SEROTONERGIC RECEPTORS IN THE EFFECTS OF MU-OPIOID IN SQUIRREL-MONKEYS RESPONDING UNDER A TITRATION PROCEDURE

This experiment was conducted to determine whether drugs acting on bra in serotonin modulate the effects of the mu opioid, morphine, as measu red by the squirrel monkey shock titration procedure and, if so, wheth er serotonergic modulation is mediated via specific 5HT receptor subty pes. Under this procedure, electric shock was delivered to the monkey' s tail and scheduled to increase once every 15 s from 0.01 to 2.0 mA i n 30 steps. Five responses on a lever during the 15-s shock period ter minated the shock for 15 s, after which the shock resumed at the next lower intensity. The intensity below which monkeys maintained shock 50 % of the time (median shock level or MSL) and rate of responding (RR) in the presence of shock were determined under control conditions and after administration of morphine alone and in combination with various serotonergic compounds. Morphine increased median shock level and dec reased rate of responding in a dose-dependent manner. These effects of morphine were attenuated by the 5HT(1A) receptor agonists, 8-OH-DPAT [(+)-8-hydroxy-2(d-n-propylamino tetralin HBr] and ipsapirone. The eff ects of morphine were not altered by the 5HT(1A) receptor antagonist, NAN-190 [1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl] piperazine HB r], the 5HT(2) receptor antagonist, ketanserin, the 5HT(3) receptor an tagonist, MDL 72222 [3-tropanyl-3,5-dichlorobenzoate], the alpha(2) ad renergic antagonist, yohimbine, or the alpha, adrenergic agonist, clon idine. These results suggest that 5HT(1A) receptors may be involved in the effects of morphine in the shock titration procedure, whereas 5HT (2), 5HT(3) and alpha(2) adrenergic receptors do not appear to play a role in morphine's effects in this procedure.