EFFECT OF OMEGA-CONOTOXIN AND VERAPAMIL ON ANTINOCICEPTIVE, BEHAVIORAL AND THERMOREGULATORY RESPONSES TO OPIOIDS IN THE RAT

This study with the rat evaluated the contribution of omega-conotoxin GVIA-(omega-CgTx) and verapamil-sensitive Ca2+ channels in behavioural , antinociceptive and thermoregulatory responses to intracerebroventri cular (i.c.v.) injection of [D-Ala2,NMePhe4Gly-ol5]enkephalin (DAMGO), [D-Pen2D-Pen5]enkephalin (DPDPE) and dynorphin A-(1-17), which are se lective agonists for putative mu, delta and kappa-opioid receptors, re spectively. The rats treated with omega-CgTx (8-32 pmol i.c.v.) showed transient, dose-dependent shaking behaviour, hyperalgesia and hypothe rmia which gradually disappeared within 4 h. The behaviour of the rats was normal by 24 h. Histological examination of brain sections showed morphological alterations of neurons in the hippocampus, medial-basal hypothalamus and pyriform cortex. Antinociception, catalepsy and ther moregulatory responses elicited by DAMGO (0.4 and 2.0 nmol) were signi ficantly prolonged and potentiated by verapamil (20 pmol i.c.v. 15 min before) or omega-CgTx (8 pmol 24 h before). Antinociception and hypot hermia induced by DPDPE were antagonized by verapamil and omega-CgTx, whereas only omega-CgTx prevented the behavioural arousal observed aft er DPDPE. Similarly, hypothermia induced by dynorphin A-(1-17) (5.0 nm ol) and by the kappa-opioid receptor agonist U50,488H (215 nmol) was a ntagonized by the two Ca2+ channel blockers but only omega-CgTx preven ted the barrel rolling and bizarre postures caused by the opioid pepti de.