Chronic Treatment with Prazosin Causes a Subtype-specific Increase in the α1-Adrenoceptor Density of the Stressed Rat Cerebral Cortex

Abstract

Abstract The effects of chronic treatment with prazosin and of immobilization stress on the α1-adrenoceptor subtypes in rat cerebral cortex have been examined. Prazosin-treated rats were allowed free access to tap water containing two different concentrations of prazosin (16 or 156 mg L−) for 5 weeks. The mean plasma concentrations of prazosin were 5 ng mL− in groups treated with a low dose and 8 or 14 ng mL− in those treated with a high dose. Immobilization stress (2 h day−, 2 weeks) or chronic treatment with a low dose of prazosin caused no significant change in the affinity for [3H]prazosin or in the maximum number of α1-adrenoceptor sites (Bmax). However, treatment with prazosin (low dose) combined with stress increased the density of α1-adrenoceptors with low affinity for prazosin. Treatment with a high dose of prazosin increased the density of α1L-adrenoceptors, irrespective of stress loading. The densities of α1A- and α1B-adrenoceptors with high affinity for prazosin were increased only after treatment with a high dose of prazosin in combination with stress. These results indicate that three distinct α1-adrenoceptor subtypes, α1A, α1B and α1L, might be affected differently by treatment with prazosin and by stress.