Retrograde axonal transport of beta-adrenoreceptors in rat brain: effect of reserpine

Abstract

Retrograde axonal transport of beta-adrenoreceptors was assessed by measuring the accumulation of binding sites for the beta-receptor ligand [125I]iodocyanopindolol [( 125I]ICP) distal to a unilateral 6-hydroxydopamine (6-OHDA) lesion placed in the ascending noradrenergic axons of the locus coeruleus. Accumulation of binding sites was linear over a 3 day period and was blocked by intracerebroventricular 6-OHDA given 1 day prior to sacrifice. A single dose of reserpine (5 mg/kg, i.p.) caused a long lasting (6-8 week) biphasic depletion of frontal cortex norepinephrine (NE) associated with increased frontal cortex binding of another beta-receptor ligand, [3H]dihydroalprenolol [( 3H]DHA), at 7-14 days, and again at 28 days post-reserpine. Unlike the changes in cortical beta-receptors, retrograde transport of [125I]ICP in presynaptic noradrenergic neurons was decreased or blocked completely at 7-14 days and at 6 weeks, and was increased to 470% and 240% of control at 21 days and 8 weeks after reserpine. Anterograde transport of [3H]DHA binding sites was measured by accumulation proximal to a 6-OHDA lesion in this pathway. This transport varied in a pattern similar to that seen for retrograde transport of [125I]ICP binding sites. These data and others suggest that presynaptic beta-receptors are regulated independently of frontal cortex beta-receptors, which appear to be located primarily on postsynaptic cells. On the other hand, the regulation of both anterograde and retrograde transport appears to be interrelated since both types of transport were altered in a similar way in the face of long-term NE depletion by reserpine.