Effect of Scopolamine on the Cerebral Accumulation of ¹⁴C-Catecholamines from ¹⁴C-Tyrosine

Abstract

The effect of the anti-muscarinic and psychotomimetic agent, scopolamine, on the accumulation of ¹⁴C-catecholamines formed from ¹⁴C-tyrosine administered intra-cerebrally to the mouse was studied. In doses from 3 to 30 mg/kg, scopolamine was found to decrease the cerebral accumulation of ¹⁴C-dopamine and ¹⁴C-norepinephrine but increase the accumulation of ¹⁴C-normetanephrine. Similar effects on ¹⁴C-catecholamine accumulation were observed when ¹⁴C-DOPA was used as substrate. These effects are causally postulated to be related to blockade of inhibitory muscarinic responses which decrease CA output. The relevance of these findings to the toxic psychosis induced by scopolamine is discussed.

The role of striatal dopaminergic mechanisms in rotational behavior induced by phencyclidine and phencyclidine-like drugs

“…A number of ex vivo studies have found that PCP increased DA turnover and metabolism in mesolimbic and mesocortical DA systems following systemic administration (Deutch et al 1987;Rao et al 1990b;Tanii et al 1990;Bristow et al 1993) while either producing decreases or having no effects in the striatum (Deutch et al 1987;Rao et al 1990b;Tanii et al 1990;Bristow et al 1993). The DA uptake inhibitory properties of PCP, on the other hand, appear to be more consistent across brain regions (Hitzemann et al 1973;Smith et al 1977;Vickroy and Johnson 1980). Such properties seem to underlie its ability to enhance extracellular levels of DA in mesolimbic (Hernandez et al 1988;Carboni et al 1989;McCullough and Salamone 1992;Steinpreis and Salamone 1993), mesocortical (Hondo et al 1994), as well as nigrostriatal (Steinpreis and Salamone 1993) systems, as assessed with in vivo microdialysis procedures.…”

Effects of phencyclidine on schedule-controlled responding following neurotoxic lesions of the striatum

“…It has also been demonstrated that non-competitive NMDA antagonists, such as phencyclidine and N-[1-(2-thienyl)cyclohexyl]piperidine (TCP), stimulate tyrosine hydroxylase activity in vitro (Vickroy and Johnson, 1981;Mateu et al, 2000). However, in vivo studies indicate that phencyclidine may actually inhibit tyrosine hydroxylase activity (Hitzemann et al, 1973;Doherty et al, 1980). Some behavioral components of the phencyclidine profile have been directly linked to phencyclidine's action on the central dopaminergic system.…”