NICOTINE ENHANCES MORPHINE-ENDORPHIN-INDUCED AND BETA-ENDORPHIN-INDUCED ANTINOCICEPTION AT THE SUPRASPINAL LEVEL IN THE MOUSE

The effect of nicotine administered supraspinally on antinociception i nduced by supraspinally administered opioids was examined in ICR mice. The intracerebroventricular (i.c.v.) injection of nicotine alone at d oses from 1 to 12 mu g produced only a minimal inhibition of the tail- flick response. Morphine (0.2 mu g), beta-endorphin (0.1 mu g), D-Pen( 2,5)-enkephalin (DPDPE; 0.5 mu g), trans-3,4-dichloro-N-methyl-N-[2-(1 -pyrrolidinyl) cyclohexyl] benzeocetamide (U50, 488H; 6 mu g) caused o nly slight inhibition of the tail-flick response. Nicotine dose depend ently enhanced inhibition of the tail-flick response induced by i.c.v. administered morphine (0.2 mu g) or beta-endorphin (0.1 mu g). The de gree of enhancing effect of nicotine toward beta-endorphin-induced inh ibition of the tail-flick response was greater than toward morphine-in duced inhibition of the tail-flick response. However, i.c.v. administe red nicotine at the same doses was not effective in enhancing the inhi bition of the tail-flick response induced by DPDPE (0.5 mu g) or U50, 488H (6 mu g) administered i.c.v. Our results suggest that stimulation of supraspinal nicotinic receptors may enhance antinociception induce d by morphine (a mu-opioid receptor agonist) and beta-endorphin (an ep silon-opioid receptor agonist) administered supraspinally. However, th e activation of nicotinic receptors at supraspinal sites may not be in volved in enhancing the antinociception induced by DPDPE (a delta-opio id receptor agonist) or U50, 488H (a kappa-opioid receptor agonist) ad ministered supraspinally.