PUTATIVE 5-HT1-LIKE RECEPTOR AGONISTS AND MORPHINE-WITHDRAWAL SYNDROME - RELATIONSHIP WITH LOCOMOTOR-ACTIVITY

The effects of two putative 5-HT1-like receptor agonists, RU 24969 and 8-OH-DPAT, were examined on withdrawal symptoms, using models of acut e and chronic morphine dependence in rats and mice. Both drugs attenua ted several behavioral symptoms of morphine withdrawal precipitated by naloxone. Similar to the naive rats, we observed an increase of locom otion by RU 24969 or 8-OH-DPAT in chronic morphine dependent rats as w ell. The locomotor activity of morphine dependent mice, though remaini ng unaffected by moderate doses, was decreased by high doses of 8-OH-D PAT and RU 24969. An attenuating effect of 5-HT1 receptor agonists on morphine withdrawal symptoms in rats and mice was observed by various concentrations of drugs, which decreased, potentiated or even did not affect the locomotor activity in animals. In addition, an administrati on of RU 24969 or 8-OH-DPAT, in doses which attenuated a naloxone prec ipitated withdrawal symptom, did not affect the naloxone induced hyper motility in morphine dependent rats and mice. Evidently, the decrease in severity of naloxone-precipitated morphine withdrawal syndrome by t he 5-HT1-like receptor agonists does not seem to be secondary to the c hanges in the motility of the animals. It is suggested that the effect s of RU 24969 and 8-OH-DPAT on the opiate withdrawal syndrome might be due to a functional inactivity (by a presynaptic action) of serotoner gic system but the unspecific effect which is unrelated to the 5-HT1-l ike receptors should not excluded.