GABAergic drugs and sexual motivation, receptivity and exploratory behaviors in the female rat

Abstract

Female rats were allowed to pace sexual interactions in a bilevel chamber, where a sexually vigorous male was tethered to the bottom level. Exploratory behaviors (sniffing, rearing), locomotor activity (expressed as number of level changes and periods of inactivity) as well as items of sexual motivation (latency to descend to the male's level, approaches towards the male and genital exploration) were recorded. In addition, sexual receptivity was evaluated in a non-paced situation. A test for motor impairment was also performed. The GABA transaminase inhibitor gamma-acetylene GABA reduced exploratory behaviors at doses much lower than those needed to reduce receptivity. The GABA reuptake inhibitor SKF 100330A did not affect any behavior category at doses of 15 and 30 mg/kg, but had a sedative action at 60 mg/kg. This was shown as impaired motor coordination and an almost total absence of activity in the bilevel chamber. Receptivity was not impaired, however. The mixed GABAA/ GABAB agonist progabide reduced exploratory behaviors and receptivity without producing motor impairment at a dose of 400 mg/kg. The GABAA agonist THIP impaired motor coordination and reduced receptivity and exploratory behaviors at a dose of 10 mg/kg. A larger dose, 20 mg/kg, had a strong sedative action. Only a small proportion of the animals descended to the males level. The GABAB agonist baclofen reduced receptivity at a dose that had no effect on motor coordination or exploratory behaviors. None of the drugs had a specific effect on sexual motivation. Whenever behaviors reflecting motivation were reduced, there were also other behavioral effects indicative of sedation. These data show that GABA receptor agonists, particularly the GABAB agonist baclofen, reduce sexual receptivity at doses that have only slight effect on motor functions or exploratory behaviors. In contrast, non-specific enhancement of GABAergic activity by a transaminase or reuptake inhibitor have effects on motor functions and exploratory behaviors at doses much lower than those needed to reduce receptivity.

GABAB receptor agonists reduce operant ethanol self-administration and enhance ethanol sedation in C57BL/6J mice

“…Therefore, reductions in self-administration could be due to the nonspecific actions of these agonists and not necessarily to decreases in the reinforcing nature of the drug of abuse. Addressing the sedative effects of baclofen are especially pertinent in alcohol self-administration studies given that, at certain doses, both baclofen and ethanol alone can have sedative and motor impairing/locomotor depressing properties (Lewis et al 1989;De Luca and Massotti 1990;Middaugh et al 1992;gmo and Soria 1997;Munzar et al 2000). Thus, co-administration of baclofen and alcohol could potentially result in enhancement of the sedative properties of either compound.…”

Studies of Sociosexual Interactions in Rats in an Externally Valid Procedure: Are They Relevant for Understanding Human Sexual Behavior?

“…There are many observations suggesting that female non-sexual behaviors are controlled differently from receptivity and paracopulatory behavior. For instance, the independence of sexual behaviors from other social behaviors has been reported by Ågmo & Soria (1997) in female rats observed in a bilevel chamber. In that study, a male rat was placed on the lower level, which allowed the female to pace sexual interactions.…”

Gabapentin increases expression of δ subunit-containing GABAA receptors

“…Gaboxadol is considered to be a “super-agonist” as it generates a current that is larger than current evoked by a saturating concentration of GABA [36]. In both humans and laboratory animals, gaboxadol, similar to gabapentin, produces anxiolysis and impairs motor coordination [[45], [46], [47], [48], [49]].…”