Sites of action of amphetamine intrinsic to catecholaminergic nuclei: catecholaminergic presynaptic dendrites and...

1. It is now well established that the behavioral actions of amphetamine, especially locomotor and stereotyped behaviors, are dependent in part upon the release of catecholamines in the central nervous system. 2. A variety of empirical evidence has established that the release of catecholamines by amphetamine leads to changes in neuronal activity in regions postsynaptic to catecholaminergic nerve terminals. In addition, release of catecholamines is accompanied by a marked inhibition of neuronal firing in catecholaminergic neurons. 3. At least two conceptions have been advanced to account for this marked decrease in catecholaminergic neuronal activity. (a) In one of these, release of catecholamines from presynaptic terminals is thought to lead to a compensatory decrease in neuronal firing rate by means of a postsynaptic neuronal feedback loop from regions innervated by catecholaminergic neurons. (b) In the other, decreased neuronal activity is hypothesized to result from local release of catecholamines onto or near catecholaminergic neuronal dendrites and somata, a phenomenon that has been characterized as self-inhibition. 4. For dopaminergic neurons, recent biochemical, neuropharmacological and neuroanatomical evidence suggests that the latter process could be subserved by dopamine released from dopaminergic neuronal dendrites, i.e., "presynaptic" dendrites.