Behavioral and biochemical studies of the scopolamine-induced reversal of neuroleptic activity

Abstract

Scopolamine reversed the reduction in avoidance responding caused by spiperone and antagonized the inhibitory effects of spiperone on the behavioral actions of d-amphetamine or apomorphine. Scopolamine-induced locomotor activity was greater in 6-hydroxydopamine (6-OHDA)-treated animals than in controls. This increase was prevented by administration of alpha-methyltyrosine, but not by inhibition of dopamine-beta-hydroxylase, indicating that this action of scopolamine was associated with presynaptic dopaminergic fibers. Therefore, the possibility that pre-synaptic dopaminergic function was the locus of the antagonism of spiperone by scopolamine was examined using drug interaction studies in 6-OHDA-treated rats. However, when 6-OHDA-treated rats were given alpha-methyltyrosine, scopolamine still reversed the spiperone blockade of apomorphine-induced locomotion. Although these data provided evidence for a post-synaptic action for this cholinergic blocking agent, scopolamine affected neither dopamine-stimulated adenylate cyclase activity nor 3H-spiperone binding in vitro. Furthermore, scopolamine did not alter the level of specific 3H-spiperone binding found in brain after in vivo administration. This suggests that the post-synaptic mechanism affected by scopolamine is different from the site affected by spiperone. Thus, it is concluded that scopolamine can affect both pre- or post-synaptic events associated with dopaminergic function and that both may contribute to the reversal of the actions of spiperone.

Priming of D1-dopamine receptor responses: long-lasting behavioral supersensitivity to a D1-dopamine agonist following repeated administration to neonatal 6-OHDA-lesioned rats

“…Scopolamine and theophylline can produce enhanced activity levels in 6-OHDA-lesioned rats, and this response appears to depend on catecholamine release from remaining neurons (Ondrusek et al, 198 1;Criswell et al, 1988). In neonatal 6-OHDAlesioned rats, the response to the first dose of these compounds was less than that seen after the compounds had been administered repeatedly for 3 doses.…”

“…Previous data indicate that scopolamine and theophylline increase the activity level in 6-OHDA-lesioned rats; this response is dependent upon endogenous catecholamine release (Ondrusek et al, 198 1;Cfiswell et al, 1988). Therefore, we chose to use these indirect-acting dopamine agonists to see if endogenous release of dopamine would prime D,-dopamine receptor responses.…”

Solanum Alkaloids and their Pharmaceutical Roles: A Review

“…In addition, the level of 3H-spiperone in brain and dopamine associated activity of adenylate cyclase remains unchanged confirming the post-synaptic association of scopolamine. 77 Solaphyllidine and desacetylsolaphyllidine from S. oblongifolium,were studied for their effects on locomotor activity (mice) i.e., both the alkaloids reduced duration of sleep, while, solaphyllidine enhanced locomotor activity. 57…”