Mr. Dzoljic et al., PUTATIVE 5-HT1-LIKE RECEPTOR AGONISTS AND MORPHINE-WITHDRAWAL SYNDROME - RELATIONSHIP WITH LOCOMOTOR-ACTIVITY, Research communications in substance abuse, 13(1), 1992, pp. 61-78
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.