Effect of cocaine sensitization on alpha1-adrenoceptors in brain regions of the rat: an autoradiographic analysis.

We investigated the effects of repeated intermittent cocaine treatment, resulting in behavioral sensitization, on the density of α 1 -adrenoceptors in the rat brain measured by quantitative in vitro autoradiography of [ 3 H]prazosin. Animals were decapitated following a short (2 h) and long (48 h) withdrawal period after an injection of cocaine (10 mg/kg) on day 10 given to either cocaine-naive (saline daily, days 1-5) or cocaine-sensitized (cocaine 10 mg/kg daily, days 1-5) rats. In cocaine-naive rats, significant decreases in α 1 -adrenoceptors 2 h after a single dose of cocaine were observed in the amygdaloid nuclei and hippocampus; the decreases in the centromedial nucleus of the amygdala persisted until 48th hour of withdrawal. On the contrary, increases in α 1 -adrenoceptors after 2-h withdrawal were seen in the nucleus accumbens core and retrosplenial cortex. In cocaine-sensitized rats, the density of α 1 -adrenoceptors 2 h after the challenge with cocaine increased in the centrolateral amygdala, while in the granular retrosplenial cortex and in the most ofthalamic nuclei, the densities of α 1 -adrenoceptors decreased. After 48-h withdrawal, the density of α1-adrenoceptors increased in the nucleus accumbens core and shell (by 21% and 58%, respectively), and in the amygdaloid centromedial and basolateral nuclei (by ca. 24%), while the decline was still observed in some thalamic nuclei. Our study shows for the first time that cocaine sensitization produces significant (dependent on the withdrawal time) alterations in the α 1 -adrenoceptor density, and the changes in some parts of the thalamus seem to be related to processes of cocaine relapses.