Pharmacological blockade of brain alpha1-adrenoceptors as measured by ex vivo [3H]prazosin binding is correlated with behavioral immobility.
The present studies examined the relationship between the blockade of central alpha1-adrenoceptors, as measured by ex vivo binding of [3H]prazosin in the cerebral cortex and the inhibition of behavioral activation to a mildly novel environment (cage change). It was found that intraventricular (i.v.t.) terazosin, a saline-soluble alpha1-adrenoceptor antagonist, dose dependently inhibited both ex vivo cortical binding and behavioral activation and that there was a highly significant positive correlation between the two with a slope near unity. Prazosin, a nonsaline soluble antagonist which had to be given intraperitoneally (i.p.), was much less potent at blocking both behavioral activity and cortical ex vivo binding, although it blocked ex vivo binding in the lung, indicating that it was effective peripherally but did not readily enter the brain. Despite this, however, the inhibition of cortical binding and behavioral activation that i.p. prazosin did produce were highly correlated with each other and had a slope near unity as with terazosin, whereas the more potent inhibition of lung binding was less well correlated with behavioral inhibition and had a slope significantly less than one. These results confirm our earlier studies, which have shown that alpha1-adrenoceptor activity is essential for gross and fine motor behavior in the mouse and that prazosin, which is used extensively in behavioral research, has difficulty entering the mouse brain.[1]References
- Pharmacological blockade of brain alpha1-adrenoceptors as measured by ex vivo [3H]prazosin binding is correlated with behavioral immobility. Stone, E.A., Rosengarten, H., Lin, Y., Quartermain, D. Eur. J. Pharmacol. (2001) [Pubmed]
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