CHOLERA-TOXIN ANTAGONIZES MORPHINE-INDUCED CATALEPSY THROUGH A CYCLICAMP-INDEPENDENT MECHANISM

We studied the effect of intracerebroventricular pretreatment with per tussis toxin and cholera toxin on morphine catalepsy in rats. Pertussi s toxin (1 mug/rat, two, three and six days before) did not affect cat alepsy evoked by central morphine. Cholera toxin (1 mug/rat) did not a ffect morphine catalepsy after 24 h and 48 h, but significantly reduce d it (about 60%) after three and five days. Ten days later the morphin e response had totally recovered. This effect was selective, since mor phine analgesia was not modified. The reduction of catalepsy appeared unrelated to the ability of cholera toxin to raise cAMP levels, as dem onstrated by the different time course of changes in striatal cholera toxin-stimulated adenylate cyclase activity. The effect required an in tact cholera toxin molecule and did not occur with a similar dose of c holera toxin-B subunit. These findings demonstrate that catalepsy is a n opioid effect not linked to pertussis toxin-sensitive G proteins and suggest that the G(s) protein might be involved.