THE ROLE OF 5-HT IN THE EXPRESSION OF MORPHINE-WITHDRAWAL IN MICE

The effects of methysergide and cyproheptadine on naloxone-precipitate d withdrawal symptoms were studied in morphine-dependent mice. The eff ects of these drugs were investigated both in normal mice and also mic e injected with 6-OHDA intracerebrally to destroy the central noradren ergic neurones and examine whether 5-HT mediated effects are somehow l inked to noradrenergic pathways. Methysergide given 30 min before nalo xone attenuated withdrawal jumping, ''wet dog'' shakes, burrowing and body weight loss but aggravated hypothermia. Similar effects were prod uced by cyproheptadine on withdrawal ''wet dog'' shakes and hypothermi a. Jumping was aggravated by low doses and attenuated by higher doses of cyproheptadine. Intracerebral injection of 6-OHDA in 5 days old mic e pups resulted in hyperlocomotion by the end of 30 days before initia tion of morphine dependence. When they were made morphine-dependent, m ice pretreated with 6-OHDA developed higher degree of naloxone-induced withdrawal jumping than non-treated mice. Methysergide further aggrav ated jumping but its effect on both ''wet dog'' shakes and burrowing w as lost in mice exposed to 6-OHDA. These findings suggest that 5-HT re ceptors are involved in the expression of withdrawal symptoms and the functional responsiveness of these receptors is dependent on intact no nadrenergic pathways.