BEHAVIORAL AND NEUROCHEMICAL SENSITIZATION OF MORPHINE-WITHDRAWN RATSTO QUINPIROLE

The sensitivity of dopamine D-2-like receptors in morphine-withdrawn r ats was studied using the selective agonist quinpirole. Morphine was a dministered twice daily increasing the daily dose from 20 to 50 mg/kg during 7 days. Twenty-four hours after the last morphine administratio n the rats were given quinpirole (0.01-1 mg/kg), and their behaviour w as assessed. Withdrawal from repeated morphine treatment enhanced yawn ing behaviour and penile erections induced by small doses (0.01-0.1 mg /kg) as well as the intensity of stereotypy induced by a large dose (1 .0 mg/kg) of quinpirole. In the morphine-withdrawn rats the dose of 1 mg/kg of quinpirole caused less yawning than in the control rats, wher eas the number of erections induced by this dose was enhanced as compa red with the control animals. In the control rats the striatal and lim bic concentrations of dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA), were not clearly affected b y the smallest dose of quinpirole. However, the small dose of quinpiro le (0.01 mg/kg) significantly reduced the levels of DOPAC and HVA in t he striatum and limbic forebrain of the rats withdrawn from morphine e ither for 24 or 48 h. These findings indicate that withdrawal from rep eated morphine treatment enhances the sensitivity of dopamine D-2-like receptors.