SPINAL GABA RECEPTORS MEDIATE BRAIN DELTA-OPIOID ANALGESIA IN SWISS WEBSTER MICE

Morphine and heroin act on supraspinal mu-opioid receptors in ICR mice to activate descending noradrenergic and serotonergic systems to inhibit the tail flick response. Antinociception induced by supraspinal [D-Pen(2,5)]-enkephalin (DPDPE, delta agonist) involves a descending system mediated by spinal gamma-aminobutyric acid, GABA(A) and GABA(B), receptors. Because in Swiss Webster mice the receptor selectivity of heroin changes to delta whereas morphine remains mu, the purpose of the present study was to determine whether this delta action of heroin was mediated spinally by GABA(A) and GABA(B) receptors. Bicuculline (GABA(A) receptor antagonist) and picrotoxin (chloride ion channel blocker) given intrathecally produced rightward shifts in the dose-response curves of DPDPE and heroin given intracerebroventricularly. Thus, spinal GABA(A) receptors were involved. Intrathecal administration of 2-hydroxysaclofen (GABA(B) receptor antagonist) also shifted the dose-response curves to the right. Thus, the antinociception produced by heroin, like DPDPE, by activation of delta receptors in the brain of Swiss Webster mice involved both GABA(A) and the GABA(B) receptors in the spinal cord.