Effect of cocaine and desmethylimipramine on the uptake, retention and metabolism of 3H-5-hydroxytryptamine in rat brain slices.

Uptake and metabolism of 3H-5-dydroxytryptamine (3H-5-HT) in slices of hypothalamus, brain stem caudate nucleus and parietal cortex were examined in vitro. The results indicate that 3H-5-HT taken up by neurons is firmly retained and that there are regional differences in the uptake and retention of 3H-5-HT. For example, the caudate had a significantly greater maximum rate of uptake and binding (Vmax) than the other brain areas tested, particularly the cortex. In contrast the caudate appeared to have the lowest apparent for 3H-5-HT uptake (Km). Uptake and retention of 3H-5-HT by four brain areas were markedly inhibited by cocaine and desmethylimipramine (DMI) in vitro. The inhibitory effect of both drugs was noncompetitive in nature, with exception of thct that cocaine and DMI failed to reduce the formation of 3H-5-hydroxy-indoleacetic acid despite ther potent blocking action of 3H-5-HT uptake suggests that a significant amount of 3H-5-HT is oxidatively deaminated at extraneouronal sites. This extraneuronal metabolism of 5-hydroxytryptamine may play an play an important role in regulating the action of this neurotransmitter.