Effect of alpha 2-adrenoceptor blockade on lithium action in the rat brain.

The inhibitory effect of different concentrations of lithium (0.15-10 x 10(-3) M) on cAMP production induced by isoprenaline (1 x 10(-4) M) after the blockade of alpha(2)-adrenoceptors in the rat cerebral cortex was investigated. Low lithium concentrations (0.3-0.6 x 10(-3) M) exerted a significant inhibitory effect after yohimbine (1 x 10(-5) M) addition, but had no effect when isoprenaline alone or prazosin (1 x 10(-7) M) was added. The recovery of [3H]yohimbine binding after irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was evaluated in cortical membranes to study how alpha(2)-adrenoceptor repopulation affects the action of lithium on the adenylyl cyclase-cAMP system. When the density of alpha(2)-adrenoceptors was lower than 21%, lithium showed a significant inhibitory effect at all concentrations tested. However, at higher densities, increased concentrations of lithium were required to inhibit cAMP production. Our results suggest that the inhibitory effect of lithium on cAMP levels in the rat brain is conditioned by alpha(2D)-adrenoceptors.