The putatively selective dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 stimulate prolactin release in rats |
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Authors: | Kjell Svensson Maria Carlsson Arvid Carlsson Stephan Hjorth Anette M. Johansson Elias Eriksson |
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Affiliation: | a Department of Pharmacology, University of Göteborg, Sweden b Department of Organic Pharmaceutical Chemistry, University of Uppsala, Sweden |
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Abstract: | The 2-aminotetralin derivatives cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76, and cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, are novel centrally acting stimulants with a putative action as selective dopamine (DA) autoreceptor antagonists. In the present study these compounds were evaluated with respect to their effects on prolactin release in male rats. Both (+)enantiomers caused a pronounced increase in plasma prolactin levels in previously untreated animals. The effects of (+)-AJ 76 and (+)-UH 232 were virtually similar, except for a higher initial increase after the latter compound. In agreement with earlier reports, the reserpine-induced elevation of plasma levels of prolactin was strongly suppressed by the DA autoreceptor agonist B-HT 920. This effect of B-HT 920 was completely blocked by (+)-AJ 76 and by (+)-UH 232, indicating that both (+)enantiomers antagonize lactotroph DA receptors. The present findings support the notion that lactotroph DA receptors resemble DA autoreceptors rather than postsynaptic DA receptors. A possible difference between the auto-/lactotroph vs. postsynaptic DA receptors with respect to both the responsiveness to agonists and to the affinity of pure antagonists is discussed. |
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Keywords: | Prolactin release Dopamine receptors Dopamine autoreceptor antagonists (Rat) |
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