Pharmacological analysis of acute morphine dependence in infant rats: close molecular relationship of head-shaking precipitated by opiate antagonists and cholinergic neurotransmission

The influence of drugs affecting different neurotransmitter systems on an acute abstinence heanshaking (AHS) model induced by nalorphine or naloxone was studied in 9-day-old rat pups pretreated (3 h before) with morphine (10mg/kg, i.p.). One hour after the injection of nalorphine (10 mg/kg, i.p.) AHS was stopped by a second dose of morphine (10 mg/kg, i.p.) and reinitiated 1 h later by a higher dose of nalorphine (20 mg/kg, i.p.). In other groups AHS was blocked by spiroperidol (0.1 mg/kg, i.p.), clonidine (0.01 mg/kg, i.p.) or scopolamine (50 mg/kg, i.p.). In these groups a second injection of nalorphine did not reinitiate AHS. In dose-effect curve experiments the AHS induced by naloxone or nalorphine was significantly reduced by previous injections of scopolamine, spiroperidol, metergoline or phentolamine in the corresponding groups. Scopolamine was the only antagonist which displaced the AHS dose-effect curves to the right without affecting the maximal response. Since no common receptors exist for a direct competitive interaction between opiate antagonists and scopolamine, these experiments suggest that a direct molecular relationship exists between the tissue concentration of nalorphine (or naloxone) and the endogenous ACh release during abstinence. Thus, the AHS model in 9-day-old rats clearly differentiates specific from non-specific blockade of the abstinence syndrome, and confirms a distinct or primary role of cholinergic neurotransmission in morphine abstinence

Effects of metoclopramide on spontaneous and pharmacologically-induced yawning in the rat

La metoclopramida (MCP) ha sido caracterizada por Alender et al. (1980) como un fármaco que tiene una acción 4 a 5 veces mayor sobre los respcetores dopaminérgicos presinápticos (autorreceptores) que sobre las postsinápticos. En este trabajo se estudia su acción sobre el bostezo espontáneo o inducido por fisostigmina (0,10 mgKg, i.p.) y apomorfina (0.05 mgKg, s.c.) en ratas machos Sprague Dawley de dos a tres meses de edad. Los efectos de la MCP se exploraron en el rango de 0.3 a 1.0 mgKg, rango en el cual el fármaco es selectivamente activo sobre los autoreceptores. Los animales se inyectaron, i.p., 15 minutos antes de la observación conductual. Se encontraron reducciones de la frecuencia del bostezo proporcionales a las dosis utilizadas, obteniéndose con la dosis máxima (1.0 mgKg), un decremento de 90% y 60%, respectivamente, en el bostezo espontáneo y el inducido con fármacos. Estos resultados son compatibles con la hipótesis de que los autorreceptores presinápticos dopaminérgicos desempeñan un papel fisiológico en la regulación del bostezo