Stereospecific actions of baclofen on sociosexual behavior, locomotor activity and motor execution

Abstract

The behavioral effects of racemic baclofen and the r and s enantiomers were studied in order to determine whether the stereospecificity found in receptor binding studies also applies to the behavioral actions of the drug. Racemic and r-baclofen inhibited sexual behavior, locomotor activity and motor execution at relatively low doses while s-baclofen was completely inactive even when a dose 40 times higher than the minimum effective dose of r-baclofen was used. The r enantiomer seems to be twice as active as racemic baclofen. These data strongly suggest that the behavioral effects of baclofen are the result of an action at the GABA-B receptor. In order to differentiate the effects of baclofen on sexual interactions from those on nonspecific social interactions, the sociosexual behavior was observed with a castrated male or a receptive female as stimulus animal. r, s-baclofen had effects only upon sociosexual interaction with a receptive female. Moreover, the inhibitory effects of baclofen were restricted to behavioral items related to sexual interactions, primarily those constituting precopulatory behaviors. Since no effect was observed in social interactions with a castrated male, it is suggested that the inhibition of sociosexual behavior is not a consequence of impairment of motor execution. Rather it appears that baclofen has a specific inhibitory effect on behaviors associated with the initiation of copulatory activity. Therefore, once initiated, sexual behavior was not significantly modified by baclofen.