Scopolamine facilitates recovery of function following unilateral electrolytic sensorimotor cortex lesions in the rat.

Following brain injury there is an excessive release of excitatory neurotransmitters that may lead to secondary cell death. Although much research has focused on glutamate-NMDA receptor interactions, acetylcholine-muscarinic receptor interactions may also prove to be important for an understanding of the pathophysiological events that lead to secondary degeneration after brain damage. Previous experiments have shown that the muscarinic receptor antagonist scopolamine facilitates recovery from very transient (1 h-10 days) behavioral deficits after fluid percussion injury. The present study extends these findings by investigating whether scopolamine can facilitate recovery from the more enduring behavioral deficits (14-60 days) that follow electrolytic lesions of the rat somatic sensorimotor cortex (SMC). Rats received unilateral lesions of the SMC and a regimen of scopolamine (1 mg/kg) or saline beginning 15 min after surgery. Following SMC lesions rats exhibited an impairment in placing the forelimb contralateral to the lesion as well as an ipsilateral somatosensory asymmetry on a bilateral tactile stimulation test. Rats treated with scopolamine showed a reduction in the initial magnitude of the contralateral placing deficit and an accelerated rate of recovery compared with saline-treated control rats. In contrast, scopolamine had no effect on recovery from the ipsilateral somatosensory asymmetry. These data are consistent with the idea that muscarinic receptor stimulation plays a role in the production of secondary brain damage, that blockade of this receptor leads to a facilitation of recovery on some behavioral tasks, and that electrolytic lesions may trigger some of the same posttraumatic events described in other models of neural trauma.

The effects of haloperidol, scopolamine, and MK-801 on amphetamine-induced increases in ascorbic and uric acid as determined by voltammetry in vivo.

Amphetamine (which enhances dopaminergic, cholinergic, and glutamatergic activity) increases release of ascorbic acid (AA) and uric acid (UA) in the caudate nucleus. In this study, linear sweep voltammetry with carbon past electrodes was used to investigate the effects of haloperidol (a DA receptor blocker), scopolamine (a muscarinic receptor blocker), and MK-801 (an NMDA receptor blocker) alone and in combination on amphetamine-induced increases in AA and UA in the caudate nucleus. Both scopolamine (0.5 mg/kg, IP) and MK-801 (0.5 mg/kg, IP) significantly reduced amphetamine-induced increases in AA. Also, scopolamine did not affect MK-801-induced reductions of amphetamine-induced increases in AA. Unexpectedly, a subthreshold dose of haloperidol (0.1 mg/kg, IP) potentiated the ability of scopolamine to block amphetamine-induced increases in AA. Therefore, the data suggest that acetylcholine release and subsequent binding to cholinergic receptors in the caudate, are components of amphetamine-induced increases in AA. In addition, scopolamine modulated haloperidol-induced reductions of amphetamine-induced increases in release of UA. Thus, our data demonstrate that cholinergic and dopaminergic systems may interact to control release of UA.