Drug‐Induced Changes in the Release of3H‐Monoamines from Field Stimulated Rat Brain Slices

Abstract

Rat cerebral cortex slices preincubated with 3 H‐noradrenaline (NA) or 3 H‐5‐hydroxy‐tryptamine (5‐HT) and neostriatal slices preincubated with 3 H‐dopamine (DA) were stimulated by an electrical field and the overflow of radioactivity determined. The effect of drugs on overflow and release from central NA, DA and 5‐HT nerve terminals was studied. Inhibition of monoamine uptake with desipramine, cocaine or chlorimipramine increases the stimulation‐induced overflow and the results indicate that at least 35%of the released monoamines may be taken up again into the monoamine nerve terminals. Activation of NA, DA and 5‐HT receptors with clonidine, apomorphine and LSD‐25 respectively seems to decrease transmitter release. Blockade of NA and DA receptors with neuroleptic drugs increases the stimulation‐induced overflow, probably due to an increased release from the NA and DA nerve terminals. It is known that drugs used in the present investigation have a nerve impulse dependent influence on the rate of synthesis and turnover of monoamines in the central nervous system, which is generally considered to be secondary to changes in nerve impulse frequency via a nervous feed‐back mechanism. However, it seems probable from the present results that the turnover changes found in vivo after these drugs may at least partly also be due to a local effect at the central monoamine synapse, possibly via a negative feed‐back mechanism.