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Rate-dependent behavioral effects of stimulation of central motoric α1-adrenoceptors: hypothesized relation to depolarization blockade

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Abstract

Aim

The purpose of this review is to clarify how central α1-adrenoceptors control behavioral activity under varying conditions of activity and stress.

Method

The literature is reviewed regarding the behavioral actions of α1-agonists and antagonists, and α2-agonists and antagonists under conditions of high and low baseline activity and stress.

Results

It was found that α1-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 α1-antagonists; and (4) a facilitation by α2-adrenoceptor agonists which produce an opposing hyperpolarization.

Discussion

To explain these findings, it is proposed that high levels of stimulation of central α1-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 α2-agonists, and to be reversed at high agonist doses by α1-antagonists.

Conclusion

Because brain α1-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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Acknowledgements

This study was supported in part by NIMH grant MH45265. The authors thank Jay Weiss for reading the paper and for helpful comments.

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  1. Department of Psychiatry MHL HN510, NYU Med Ctr, 550 First Ave, New York, NY, 10016, USA

    Eric A. Stone

  2. Department of Neurology, New York University School of Medicine, New York, NY, USA

    David Quartermain

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Correspondence to Eric A. Stone.

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Stone, E.A., Quartermain, D. Rate-dependent behavioral effects of stimulation of central motoric α1-adrenoceptors: hypothesized relation to depolarization blockade. Psychopharmacology 178, 109–114 (2005). https://doi.org/10.1007/s00213-004-2125-y

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  • DOI: https://doi.org/10.1007/s00213-004-2125-y

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