Suppression by GABAergic drugs of the locomotor stimulation induced by morphine, amphetamine, and apomorphine: evidence for both pre- and post-synaptic inhibition of catecholamine systems

Abstract

Locomotor stimulation induced in mice by morphine and amphetamine was antagonized by pretreatment with gamma-butyrolactone (GBL) and amino-oxyacetic acid (AOAA) at doses which had little effect on saline treated animals. The effects of morphine and AOAA on the turnover of brain catecholamines (CA) were determined by measuring both the accumulation of dopa after inhibition of central aromatic L-amino acid decarboxylase and by measuring the depletion of noradrenaline (NA) after inhibition of tyrosine hydroxylase by alpha-methyltyrosine (alpha-MT). Morphine and AOAA were found to have opposite effects on CA turnover, i.e. morphine caused an increase and AOAA, a decrease. AOAA also antagonized the morphine-induced increase in CA turnover. These data might suggest that the well documented ability of GABAergic drugs to inhibit the firing of DA-containing neurons may be of importance in explaining the present findings. However, the locomotor stimulation induced by the directly-acting CA agonists, apomorphine and clonidine after pretreatment with reserpine and alpha-MT was also inhibited by the GABAergic drugs. It is therefore concluded that the suppressant effects of the GABAergic agents on hypermotility and not solely mediated by their effects on presynaptic CA mechanisms, but also by a postsynaptic inhibition at some point beyond the CA neurons.