Effect of ω-conotoxin and verapamil on antinociceptive, behavioural and thermoregulatory responses to opioids in the rat

Abstract

This study with the rat evaluated the contribution of ω-conotoxin GVIA-(ω-CgTx) and verapamil-sensitive Ca 2+ channels in behavioural, antinociceptive and thermoregulatory responses to intracerebroventricular (i.c.v.) injection of [ D- Ala 2,NMePhe 4,Gly-ol 5]enkephalin (DAMGO),[ D-Pen 2, D-Pen 5]enkephalin (DPDE) and dynorphin A-(1–17), which are selective agonists for putative μ, δ and κ-opioid receptors, respectively. The rats treated with ω-CgTx (8–32 pmol i.c.v.) showed transient, dose-dependent shaking behaviour, hyperalgesia and hypothermia 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 thermoregulatory responses elicited by DAMGO (0.4 and 2.0 nmol) were significantly prolonged and potentiated by verapamil (20 pmol i.c.v. 15 min before) or ω-CgTx (8 pmol 24 h before). Antinociception and hypothermia induced by DPDPE were antagonized by verapamil and ω-CgTx, whereas only ω-CgTx prevented the behavioural arousal observed after DPDPE. Similarly, hypothermia induced by dynorphin A-(1–17) (5.0 nmol) and by the κ-opioid receptor agonists U50,488H (215 nmol) was antagonized by the two Ca 2+ channel blockers but only ω-CgTx prevented the barrel rolling and bizarre postures caused by the opioid peptide.