Interactions between the NMTs Are Common

Many of the results of the behavioral studies cited previously are interpreted as though a single NMT system was affected by the experimental drug. These interpretations are true in an approximate sense only. Even if drugs bind tightly and selectivity to a single receptor (they frequently do not), more than one neuroactive substance may be affected through simple postsynaptic effects and reuptake mechanisms. For example, if NA is infused into cortical tissue-containing cells and axon terminals of DA neurons, micro-dialysis of that tissue records increases in both NA and DA. The NA increase is expected since it was added by the experimenter. However, what caused the increase in DA? The increase cannot be caused by the action of NA on receptors on dopaminergic cell bodies because none are present. The answer is that both NA and DA are recycled into the presynaptic terminal of the DA neuron, which causes the synaptic release of DA to increase. Thus, drugs applied by the systemic route are likely to interact with several neurotransmitter systems. Indeed, there are only a few instances in which a single transmitter fails to affect all other transmitters.

Other examples of cross talk can be found between cholinergic and monoaminergic systems. For example, applications of nicotine in the vicinity of the axon terminals of noradrenergic neurons facilitate noradre-nergic release and glutamatergic neurotransmission. In addition, GABA, an inhibitory neurotransmitter, exerts tonic inhibition on the cholinergic system. Lastly, both DA and SE regulate the release of ACH in the cortex.

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