Rate-dependent behavioral effects of stimulation of central motoric alpha(1)-adrenoceptors: hypothesized relation to depolarization blockade.
OBJECTIVE
The purpose of this review is to clarify how central alpha(1)-adrenoceptors control behavioral activity under varying conditions of activity and stress.


METHODS
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Stone
Eric A
EA
Department of Psychiatry MHL HN510, NYU Med Ctr, 550 First Ave, New York, NY 10016, USA. es35@nyu.edu
Quartermain
David
D
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D006801:Humans; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D018340:Receptors, Adrenergic, alpha-1