Effects of baclofen on different dopaminergic neuronal systems

Abstract

Systemic administration of dl or l-baclofen causes a dose-related increase in the concentration of dopamine (DA), but not of norepinephrine, in the forebrains of mice and rats. Microinjections of baclofen or GABA into substantia nigra increase DA in striatum. Since only the effect of GABA is reversed by picrotoxin, it would appear that baclofen does not act through a GABAergic mechanism. Baclofen-induced changes in DA concentrations are believed due to the depression of neuronal impulse flow which results in a decreased release of DA and thus a concomitant decrease in putative autoreceptor activation. Activation of DA autoreceptors appears to inhibit the synthesis and release of DA. Baclofen increases the concentration and the rate of synthesis of DA (accumulation of DOPA after inhibition of decarboxylase with NSD 1015) in the striatum, olfactory tubercle and posterior pituitary, but not in the median eminence. Apomorphine reverses the baclofen-induced increases in the concentration and synthesis of DA in all brain regions except median eminence, presumably by activating DA autoreceptors. Since baclofen depresses the α-methyltyrosine-induced decline of DA in all brain regions it would appear that tuberoinfundibular nerves, which terminate in the median eminence, differ from other DA nerves in that they are not regulated by autoreceptors.