Catecholamine-blocking drugs injected at sites of amine accumulation reverse catecholamine degeneration associated deficits

Abstract

It has been hypothesized that catecholamine (CA) accumulation in the axons of degenerating neurons may represent areas of functional neurotransmitter, and may be producing some of the consummatory and locomotory deficits which occur after central CA-depleting lesions. To test this hypothesis further, haloperidol (0.5 μl of a 7 nM sol.), propranolol (0.5 μl of a 175 nM sol.) or isotonic saline (0.5 μl) were injected 1.5 h, 24 h and 48 h after the injection of 6-hydroxydopamine (6-OHDA; 2 μl of 8 μg/μl) into the lateral hypothalamus (LH) of Sprague-Dawley rats to determine if the hypothermia, motor impairment and consummatory deficits could be reversed. Although haloperidol injection significantly enhanced the hypothermia seen 1.5 h after 6-OHDA injection, open field performance and consummatory responses were significantly improved after haloperidol was injected into the LH where accumulation is known to occur. Three consecutive days of intracerebral haloperidol treatment produced a recovery of body weight regulation lasting for 6 days. Treatment with propranolol enhanced open field performance 1 day after 6-OHDA injection but failed to enhance recovery of consummatory behaviour and body weight control. These results suggest that CA released from areas of accumulation act on adjacent CA receptors to participate in the production of behavioural deficits previously attributed only to the loss of functional neurotransmitter in terminal fields in the forebrain.