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Journal of Psychopharmacology
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Specific {alpha}2-adrenoreceptor antagonists induce behavioural activation in the rat

Stephen L. Dickinson

Reckitt and Colman Psychopharmacology Unit, The School of Medical Sciences, University Walk, Bristol, BS8 1TD

Brian Gadie

Reckitt and Colman Pharmaceuticals, Dansom Lane, Kingston-upon-Hull, HU8 7DS, UK

Ian F. Tulloch

Reckitt and Colman Pharmaceuticals, Dansom Lane, Kingston-upon-Hull, HU8 7DS, UK

The behavioural effects of the specific and selective {alpha}2-adrenoreceptor antagonists, idazoxan, efaroxan and RX811059, have been investigated in the rat. All three drugs induced periods of behavioural activation characterized by increased locomotion and exploration (rearing and hole dipping). However, these effects were only apparent in animals which were fully habituated to their environments and thus displayed low baseline activity. The behaviour observed lay within the normal range of activity and was not apparent under conditions when exploration was stimulated such as in a novel environment. {alpha} 2-Adrenoreceptor antagonist- induced activation was a weak response when compared with the intense and prolonged hyperactivity, in both novel and non-novel environments, induced by the amine releaser D- amphetamine. Possible mechanisms involving a direct action of noradrenaline at postsynaptic {alpha} 1-adrenoreceptors (subsequent to enhanced presynaptic {alpha}2-receptor feedback blockade) or an indirect action of {alpha}2-antagonists on dopamine function in mesolimbic pathways are discussed.

Journal of Psychopharmacology, Vol. 4, No. 2, 90-99 (1990)
DOI: 10.1177/026988119000400207
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