Chronic reserpine administration selectively up-regulates β 1- and α 1b-adrenergic receptors in rat brain: An autoradiographic study

Abstract

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 β-adrenergic receptors was measured with [ 125I]iodocyanopindolol, and binding selective for β 1and β 2subtypes was assessed by including non-radioactive drugs /that selectively mask β receptor subtypes. Total α 1-adrenergic receptor binding was measured with [ 3H]prazosin, while α 1abinding was measured with [ 3H]WB4101 (in the presence of unlabeled serotonin). Quantitative densitometric analysis revealed that chronic reserpine treatment caused an increase in β binding throughout the brain, including the cortex, thalamus, amygdala, hippocampus, caudate-putamen and hypothalamus. This effect of reserpine was entirely confined to the β 1subtype in all regions examined. [ 3H]Prazosin binding (α 1aplus α 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 α 1receptors is limited to the α 1bsubtype. The increase in α 1bbinding after reserpine administration in rats was generally smaller and less widespread than that seen with β 1binding. Thus the effect of reserpine upon noradrenergic neurotransmission demonstrates a high degree of receptor specificity and regional selectivity.