Chronic reserpine administration selectively up-regulates beta 1- and alpha 1b-adrenergic receptors in rat brain: an...

Rats were treated for 15 days with reserpine or vehicle. One day after the last treatment, animals were killed and frozen brain sections were prepared for in vitro autoradiography. Binding to beta-adrenergic receptors was measured with [125I]iodocyanopindolol, and binding selective for beta 1 and beta 2 subtypes was assessed by including non-radioactive drugs that selectively mask beta receptor subtypes. Total alpha 1-adrenergic receptor binding was measured with [3H]prazosin, while alpha 1a binding was measured with [3H]WB4101 (in the presence of unlabeled serotonin). Quantitative densitometric analysis revealed that chronic reserpine treatment caused an increase in beta binding throughout the brain, including the cortex, thalamus, amygdala, hippocampus, caudate-putamen and hypothalamus. This effect of reserpine was entirely confined to the beta 1 subtype in all regions examined. [3H]Prazosin binding (alpha 1a plus alpha 1b) was also increased after chronic reserpine in several regions of the cortex and thalamus, as well as the ventral hippocampus and caudal amygdala. No effect of chronic reserpine was seen on [3H]WB4101 binding, indicating that the effect of reserpine on alpha 1 receptors is limited to the alpha 1b subtype. The increase in alpha 1b binding after reserpine administration in rats was generally smaller and less widespread than that seen with beta 1 binding. Thus the effect of reserpine upon noradrenergic neurotransmission demonstrates a high degree of receptor specificity and regional selectivity.