Rate-dependent behavioral effects of stimulation of central motoric alpha(1)-adrenoceptors: hypothesized relation to
Eric A Stone1, David Quartermain
1Department of Psychiatry MHL HN510, NYU Med Ctr, 550 First Ave, New York, NY 10016, USA. es35@nyu.edu
Aim:
The purpose of this review is to clarify how central alpha(1)-adrenoceptors control behavioral activity under varying conditions of activity and stress.
Method:
The literature is reviewed regarding the behavioral actions of alpha(1)-agonists and antagonists, and alpha(2)-agonists and antagonists under conditions of high and low baseline activity and stress.
Results:
It was found that alpha(1)-receptor stimulation of active behavior has a number of similarities to rate dependency including: (1) a dependence on low-active, low-stress conditions or on the prior depletion of endogenous brain catecholamines; (2) a nonmonotonic dose-response relationship with high doses producing a fall-off or actual depression of activity; (3) a failure to be blocked at high agonist doses by alpha(1)-antagonists; and (4) a facilitation by alpha(2)-adrenoceptor agonists which produce an opposing hyperpolarization.
Discussion:
To explain these findings, it is proposed that high levels of stimulation of central alpha(1)-receptors produce, in host neurons, a depolarization block that impedes nerve impulse generation and inhibits active behavior. This effect is assumed to be precluded or mitigated by low-active, low-stress conditions, depletion of brain catecholamines, and by hyperpolarizing alpha(2)-agonists, and to be reversed at high agonist doses by alpha(1)-antagonists.
Conclusion:
Because brain alpha(1)-receptors are not only involved in motor activity but also in the mechanism of action of antidepressant and stimulant drugs, arousal, anxiety, stress and psychosis, a depolarization block from intense stimulation of these receptors could have broad psychopharmacological consequences and underlie rate dependency to a variety of stimulant drugs.
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