Portal de Periódicos da CAPES

Inhibition of Baclofen on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity

2001; Elsevier BV; Volume: 43; Issue: 4 Linguagem: Inglês

10.1006/phrs.2000.0789

1096-1186

Sang-Hee Woo, Hack-Seang Kim, Jae-Suk Yun, Myung-Koo Lee, Ki-Wan Oh, Yeon-Hee Seong, Seikwan Oh, Choon‐Gon Jang,

Pain Mechanisms and Treatments

The effects of baclofen on the development of reverse tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine were examined in mice. A single administration of morphine induced hyperactivity and the morphine-induced hyperactivity was inhibited dose dependently by the administration of a GABABreceptor agonist, baclofen (1.25, 2.5 and 5 mg kg−1, i.p.). Daily repeated administration of morphine developed reverse tolerance to the hyperactivity of morphine. The concomitant administration of baclofen inhibited the morphine-induced hyperactivity and the baclofen administration prior to and during the chronic administration of morphine in mice inhibited the development of reverse tolerance to the hyperactivity of morphine (10 mg kg−1, s.c.). Postsynaptic dopamine receptor supersensitivity was also developed in reverse-tolerant mice that had received the same morphine. The development of postsynaptic dopamine receptor supersensitivity was evidenced by the enhanced ambulatory activity of apomorphine (2 mg kg−1, s.c.). Baclofen also inhibited the development of postsynaptic dopamine receptor supersensitivity induced by the chronic administration of morphine. These results suggest that the hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine may be modulated via the activation of GABABreceptors induced by baclofen.