GABA Receptors in the Medial Preoptic Area Modulate the Onset of Oestradiol-Induced Maternal Behaviour in Hysterectomised-Ovariectomised, Pregnant Rats.

We studied the participation of GABA neurotransmission in the medial preoptic area (mPOA) with respect to the onset of the pup retrieval response and nest building. Pregnant female rats were implanted with bilateral cannulae in the mPOA on day 12 of pregnancy and, on day 16, the females were hysterectomised and ovariectomised and given 200 µg/kg of oestradiol benzoate. Two days later, the females received one of the following intracerebral drug treatments: GABAB agonist baclofen (200 ng); GABAB antagonist phaclofen (1 µg); GABAA antagonist bicuculline (60 ng); or physiological saline. Five minutes after intracerebral infusion, three foster pups were introduced into the females' home cage. The subjects were observed for pup grouping (retrieval) during 15 min, after which the pups were left with the female. During the next 12 h, an observation was made every 1 h to determine whether the pups had been grouped (retrieved) or not. The GABAB agonist baclofen reduced the proportion of females retrieving pups from 4 to 8 h following pup introduction. By contrast, both the GABAA antagonist bicuculline and the GABAB antagonist phaclofen enhanced the proportion of females retrieving pups during the first 3 h of observation. The latency to pup retrieval in subjects treated with the GABAB agonist baclofen was significantly longer than that in subjects given any of the antagonists. All females built a nest but baclofen reduced nest quality. These data show that activation of GABAB receptors in the mPOA has an inhibitory effect on basic maternal behaviours, whereas blockade of either the GABAA or GABAB receptor facilitates pup retrieval. It is possible that reduced GABAergic tone in the mPOA is a key element in the initiation of maternal behaviours in postparturient rats.

Role of Oestrogen α Receptors in Sociosexual Behaviour in Female Rats Housed in a Seminatural Environment.

The present study investigated the role of oestrogen receptor (ER)α in the ventromedial nucleus of the hypothalamus (VMN), the preoptic area (POA), the medial amygdala (MePD) and the bed nucleus of stria terminalis (BNST) in sociosexual behaviour in female rats. This was conducted in two sets of experiments, with the VMN and POA investigated in the first set, and the MePD and BNST in the second set. The VMN and POA received intense projections from the MePD and BNST. We used a short hairpin RNA encoded within an adeno-associated viral vector directed against the gene for ERα to reduce the number of ERα in the VMN or POA (first set of experiments) or in the BNST or MePD (second set of experiments) in female rats. The rats were housed in groups of four ovariectomised females and three males in a seminatural environment for 8 days. Compared with traditional test set-ups, the seminatural environment provides an arena in which the rats can express their full behavioural repertoire, which allowed us to investigate multiple aspects of social and sexual behaviour in groups of rats. Behavioural observation was performed after oestrogen and progesterone injections. A reduction of ERα expression in the VMN or POA diminished the display of paracopulatory behaviours and lordosis responses compared to controls, whereas the lordosis quotient remained unaffected. This suggests that ERα in the VMN and POA play an important role in intrinsic sexual motivation. The reduction in ERα did not affect the social behaviour of the females, although the males sniffed and pursued the females with reduced ERα less than the controls. This suggests that the ERα in the VMN and POA is involved in the regulation of sexual attractiveness of females. The ERα in the MePD and BNST, on the other hand, plays no role in sociosexual behaviour.

Effects of chronic treatment with the eNOS stimulator Impaza on penis length and sexual behaviors in rats with a high baseline of sexual activity.

Endothelial nitric oxide synthase (eNOS) has an important role in erection, and it also affects aspects of sexual behavior. In this experiment, we determined whether a compound enhancing the activity of eNOS, Impaza, could stimulate any aspect of sexual behavior and increase penis length in rats with a high baseline of sexual activity. For comparison, the PDE5 inhibitor sildenafil was included. Male rats were orally treated with Impaza or sildenafil for 28 days. Impaza (3 ml kg(-1)) was given daily while sildenafil (3 mg kg(-1)) was given twice weekly. Tests for sexual incentive motivation and copulatory behavior were performed just before drug treatment and at days 7, 14 and 28 of treatment. In addition, the length of the protruding penis at mount, intromission and ejaculation was measured. Impaza but not sildenafil increased penis length at mount after 14 and 28 days of treatment. The compounds failed to modify sexual incentive motivation or copulatory behavior. It is suggested that Impaza enhanced intracavernous pressure, as such a pressure increase is the most likely explanation for enhanced penis length at mount. This effect, together with an absence of motivational actions, suggests that Impaza may be the most valuable treatment for erectile dysfunction.

Inactivation of the medial preoptic area/anterior hypothalamus by lidocaine reduces male sexual behavior and sexual incentive motivation in male rats.

Permanent bilateral lesions of the medial preoptic area anterior hypothalamus (MPOA/AH) produce a drastic inhibition of male sexual behavior in all species studied to date. The present experiment was designed to evaluate if temporal inactivation of the MPOA/AH by infusions of lidocaine also inhibits sexual behavior in male rats. This would allow us to rule out the possibility that the behavioral effects observed after damage of the MPOA/AH could be associated with plastic changes induced by the lesion in other brain regions. We also evaluated sexual incentive motivation in males after the infusion of lidocaine in a test in which copulation is not possible but where males maintain approach behavior to the estrous females despite repeated testing. The percentage of animals displaying mounts, intromissions and ejaculation was significantly reduced while mount and intromission latency were prolonged after infusion of lidocaine. No changes were observed in sexual behavior after infusion of lidocaine in animals with cannulae outside the MPOA/AH suggesting that the inhibitory effects are specific to this brain region. Sexual incentive motivation was also affected by administration of lidocaine. Males consistently showed a clear preference for the sexually receptive female except when infused with lidocaine. After the infusion of the compound a significant reduction in the time spent in the incentive zone of the stimulus female was observed. These results support the hypothesis that neurons of the MPOA/AH are involved in the control of male sexual motivation.

Social and sexual incentive properties of estrogen receptor alpha, estrogen receptor beta, or oxytocin knockout mice.

Social and sexual incentive motivation, defined as the intensity of approach to a social and a sexual incentive, respectively, were studied in female Swiss Webster mice. In the first experiment, the social incentive was a castrated mouse of the same strain as the females, whereas the sexual incentive was an intact male mouse of the same strain. Ovariectomized females were first tested after oil treatment and then after administration of estradiol benzoate + progesterone in doses sufficient to induce full receptivity. The hormones increased sexual incentive motivation while leaving social incentive motivation unaffected. This suggests that sexual incentive motivation in the female mouse is dependent on ovarian hormones. In the next experiment, ovariectomized females were tested with an intact, male estrogen receptor alpha knockout and its wild type as incentives, first without hormones and then when fully receptive. There were no differences in incentive properties between the wild type and the knockout. In a similar experiment, we used an intact male estrogen receptor beta knockout and its corresponding wild type as incentives. The wild type turned out to be a more attractive social incentive than the knockout, while they were equivalent as sexual incentives. Finally, an intact male oxytocin knockout and its wild type were used as incentives. The knockout turned out to be a superior incentive, particularly a superior sexual incentive. The fact that the estrogen receptor beta and oxytocin knockouts have incentive properties different from their wild types may be important to consider in studies of these knockouts' sociosexual behaviors.

Oxytocin and estrogen receptor alpha and beta knockout mice provide discriminably different odor cues in behavioral assays.

Social behavior involves both the recognition and pro-duction of social cues. Mice with selective deletion(knockout) of either the gene for oxytocin (OT) or genes for the estrogen receptor (ER) -c or -B display impaired social recognition. In this study we demonstrate that these gene knockout mice also provide discriminably different social stimuli in behavioral assays. In an odor choice test, which is a measure of social interest and discrimination, outbred female Swiss-Webster mice discriminated the urine odors of male knock-outs IKO: OTKO, alphaERKO, betaERKO) from the odors of their wildtype littermates (WT: OTWT, alphaERWT, betaERWT). Females showed marked initial choices of the urine odors of OTWT and betaERWT males over those of OTKOand PERKO males, and alphaERKO males over alphaERWT males. The odors of OTKO and betaERKO males also induced aversive, analgesic responses, with the odors of WTs having no significant effects. Odors of both the alphaERWT andalphaERKO males induced aversive, analgesic responses,with the odors of the WT inducing significantly greater analgesia. The odors of restraint stressed WT and KO males also elicited analgesia with, again, females dis-playing significantly greater responses to the odors of stressed OTKO and betaERKO males than their WTs, and significantly lower analgesia to the odors of stressedalphaERKO than alphaERWT males. These findings show that the KO mice are discriminated from their WTs on the basis of odor and that the various KOs differ in the relative attractiveness/aversiveness of their odors. Therefore, in behavioral assays one causal route by which gene inactivation alters the social behavior of knockout mice may be mediated through the partners'modified responses to their odors.

Impaired discrimination of and aversion to parasitized male odors by female oxytocin knockout mice.

A major cost of social behavior is the increased risk of exposure to parasites, with animals utilizing social information to recognize and avoid infected conspecifics. In mice, females can discriminate between infected and uninfected males on the basis of social cues, displaying aversive responses to the odors of infected males. In the present study, using female mice whose gene for oxytocin (OT) has been selectively deleted (OT knockout mice (OTKO)), we show that at least one normal allele for OT is required for the mediation of the recognition and avoidance of parasitized males. Female wild type (OTWT) and heterozygous (OTHZ) mice distinguished between the odors of individual males infected with the louse, Polyplax serrata, and uninfected males while the KO mice did not. Exposure to the odors of infected males induced analgesia in OTWT and OTHZ females, with OTKO females displaying attenuated analgesia. OTWT and OTHZ females, but not the OTKO females, also distinguished between the odors of novel and familiar infected males and modulated their analgesic responses on the basis of prior familiarity. In an odor choice test, OTWT and OTHZ females displayed a marked initial choice for the odors of uninfected males, whereas the OTKO females showed no consistent choice. This impairment was specific to the odors of infected males. OTKO females displayed normal analgesic responses to another aversive social odor, that of a stressed male, and an aversive non-social odor, that of a cat. The OTKOs had normal non-social olfactory memory, but were impaired in their social odor memory. These findings indicate that a normal OT gene comprises an essential part of the central recognition mechanism whereby females can both reduce the transmission of parasites to themselves and select for parasite-free males.

Serotonin and sexual behavior in the male rabbit.

Sexual behavior was evaluated in sexually experienced male rabbits after the administration of different serotonergic drugs. The serotonin1A receptor agonist 8-OH-DPAT, 1 mg/kg, inhibited male rabbit sexual behavior when animals were tested 15 min after subcutaneous (SC) administration of this compound. Lower doses, 0.25 and 0.5mg/kg, were ineffective at a test 30 min after drug injection. Furthermore, 8-OH-DPAT, 0.25mg/kg, failed to revert the inhibitory effects upon sexual behavior produced by lidocaine application to the rabbit penis. Stimulation of 5-HT1B/2C receptors by TFMPP, at doses between 0.625 and 2.5 mg/kg, produced a drastic inhibition of sexual behavior when the drug was administered SC 30 min before behavioral observation. Doses below 5mg/kg were ineffective when given intraperitoneally 15 min before test. When the 5-HT1D/2C receptors were stimulated by the agonist mCPP a reduced number of mounts and ejaculations was observed after the SC administration of 1.25 and 2.5 mg/kg. Similarly, the mixed 5-HT agonist/antagonist lisuride reduced the percentage of rabbits displaying mounting behavior at doses of 0.25 and 0.5 mg/kg SC. All compounds tested produced a clear inhibition of male rabbit sexual behavior independently of the receptor subtype activated. These results are at variance with previous observations in rats where 8-OH-DPAT and lisuride produced a drastic facilitation of masculine coital behavior. Moreover, while the inhibition of male sexual behavior in rats produced by TFMPP and mCPP is associated with a disruption of the execution of this behavior, in rabbits these compounds reduced sexual motivation. These results indicate that the effects of serotonergic drugs on sexual behavior are species specific.

Naloxone potentiates anxiolytic-like actions of diazepam, pentobarbital and meprobamate but not those of Ro19-8022 in the rat.

The elevated plus-maze test was used to determine if the opiate antagonist naloxone could potentiate the anxiolytic-like effects of the benzodiazepine diazepam, the barbiturate pentobarbital, the propanediol carbamate meprobamate and the partial benzodiazepine receptor agonist [R]-1-[(10-chloro-4-oxo-3-phenyl-4H-benzo[a]quinolizin-1-yl) carbonyl]-2-pyrrolidine-methanol (Ro19-8022) in the rat. A subeffective dose of each of these compounds was combined with naloxone, 10 mg/kg. Naloxone had no effect by itself, but potentiated all drugs except Ro19-8022. The proportion of entries on the open arm increased while the total number of arms entries was not modified. These results coincide with and extend data previously obtained in the mouse. One possible explanation for naloxone's effect could be that it blocks opioid inhibition of GABAergic (gamma-aminobutyric acid) neurons thereby enhancing the effects of benzodiazepines. Another possibility is that naloxone blocks opioid effects on adenosinergic systems.

Anxiolytic-like effects of meprobamate. Interactions with an opiate antagonist in Swiss and BALB/c mice.

Naloxone has previously been shown to block the effects of benzodiazepines in the Swiss but not in the BALB/c strain. We have also reported that naloxone potentiates subeffective doses of benzodiazepines in Swiss mice. In the present studies we first determined whether naloxone could block anxiolytic-like effects of meprobamate in Swiss and BALB/c mice. Then we evaluated if subeffective doses of meprobamate could be potentiated in Swiss as well as in BALB/c mice. The elevated plus-maze test and the light/dark choice procedure were used. The lowest dose of meprobamate with anxiolytic-like effects was 60 mg/kg in the BALB/c mice. This dose was effective in both the plus-maze and in the light/dark choice procedure. In Swiss mice the same dose was effective in the plus-maze, whereas 120 mg/kg was required in the light/dark choice procedure. When an effective dose of meprobamate was combined with naloxone, 10 mg/kg, no blockade of anxiolytic-like effects was obtained in any strain in any procedure. To the contrary, when a subeffective dose of meprobamate was combined with naloxone, 10 mg/kg, an anxiolytic-like effect was obtained in both strains in both procedures. The present series of experiment shows that the ability of naloxone to block anxiolytic-like drug effects do not apply to meprobamate. However, the naloxone-induced potentiation of subeffective doses previously observed after treatment with benzodiazepines or buspirone was present also after treatment with meprobamate. Moreover, although blockade of anxiolytic-like drug effects with naloxone has not been observed in BALB/c mice, potentiation was as evident in that strain as in the Swiss. This suggests that the mechanisms behind naloxone's blockade of anxiolytic-like effects are independent from those behind its potentiation of such effects.

International Behavioral Neuroscience Society - ninth annual meeting.

The main thrust of the meeting was, as always, basic research in behavioral neuroscience defined in a broad sense. Learning and memory, feeding and drinking, reward mechanisms, development of the CNS, anxiety and stress were the main topics covered. In a public lecture associated with the meeting, Larry Reid (Rensselaer Polytechnic Institute, Troy, NY, USA) reviewed the quite compelling evidence in favor of the effectiveness of naltrexone for preventing relapse in former alcoholics. He also presented preclinical data demonstrating the remarkable effects of naltrexone given together with isradipine (Novartis AG) in blocking the rewarding effects of cocaethylene. This combination of drugs could thereby constitute a treatment for alcoholism complicated by cocaine abuse. Of potential therapeutic interest was also the description of the preclinical pharmacology and a phase II trial of a new cholinesterase inhibitor, methanesulfonyl fluoride (University of Texas). The possible physiological functions of sigma opioid receptors and the pharmacological properties of sigma receptor ligands were discussed at one of the symposia. Among the subjects covered were the potential use of sigma1 antagonists in the treatment of cocaine addiction and the efficiency of sigma1 agonists for preventing the decline in cognitive functions associated with old age.

Sexual motivation--an inquiry into events determining the occurrence of sexual behavior.

For the individual engaged in it, sexual behavior has no finality or purpose other than its own execution. Data are presented showing that the execution of sexual reflexes can promote learning, i.e. it functions as reinforcement. Furthermore, positive affect is generated. Based on these principles, a model of sexual motivation has been elaborated. The conceptual framework is the incentive motivation theory previously proposed by Bindra D, A motivational view of learning, performance, and behavior modification, Psychol Rev 1974: 81:199-213; A Theory of Intelligent Behavior, New York: Wiley, 1976; How adaptive behavior is produced: a perceptual-motivational alternative to response reinforcement, Behav Brain Sci 1978; 1:41-52. Although the model is intended for application to most mammals, the rat is used as example. Essentially, sexual approach behaviors are activated by appropriate incentives (conditioned in the male, unconditioned in the female). Approach is, in the inexperienced male, followed by the execution of copulatory reflexes as a consequence of accidentally obtained tactile stimulation of the perineal region. In the female, copulatory acts are activated by tactile stimulation of the flanks and hinds provided by the mounting male. The role of conditioning for the execution of copulatory reflexes and for the acquisition of incentive value of neutral stimuli is analyzed. It is also shown that the incentive properties of sexual acts are not substantially different from those of other incentives. Sexual exhaustion is suggested to be either a case of negative alliesthesia or of stimulus habituation and the Coolidge effect is, in consequence, an example of dishabituation. Studies in women and men support this proposal. It is emphasized that sexual behavior is best understood as being entirely mechanistic albeit not deterministic.

The duration of the effects of a single administration of dopamine antagonists on ambulatory activity and motor coordination.

Pimozide, cis(Z)-flupenthixol, SCH 23390 and sulpiride were administered to male rats. Each subject received a single drug injection, and tests for ambulatory activity and motor coordination were performed 1, 24, 48 and 72 hrs later. All drugs reduced ambulatory activity at the test 1 hr postinjection. Pimozide and SCH 23390 continued to reduce ambulatory activity at the test 24 hrs after injection. All drugs impaired motor coordination 1 hr after injection and, with the exception of SCH 23390, were also effective at the 24 hrs test. Flupenthixol, 2 mg/kg, continued to impair motor coordination also at the 48 hrs test. These data show that effects of dopamine antagonists on motor functions may persist for much longer than is generally believed. That should be important to take into account in experimental designs where repeated drug administration is employed.

GABAergic drugs and sexual behaviour in the rabbit: evidence for species-specific effects.

The effects of gamma-amino butyric acid (GABA)-ergic drugs on male rabbit sexual behaviour have been evaluated. The GABA(A) agonist 4,5,6,7-tetrahydroxixazolo-5,4c-pyridin-3-ol (THIP), the GABA(B) agonist R-baclofen and the GABA antagonists picrotoxin and bicuculline were used. Injection of THIP, 20 mg/kg, s.c. produced a complete suppression of sexual behaviour and R-baclofen, 2.5 mg/kg, s.c. a significant inhibition. Intraperitoneal injections produced effects at higher doses than did s.c. injections. The inhibition produced by R-baclofen was associated with strong motor effects as shown by the water escape test. It is probable, therefore, that the reduced sexual behaviour observed after treatment with this drug is a consequence of sedative or muscle relaxant effects. By contrast, the dose of THIP that inhibited sexual behaviour had no effect on the water escape test. These results show that the GABA(A) agonist inhibits sexual behaviour in the male rabbit independent of effects on the motor system. The GABA antagonists had marginal or no effects on sexual behaviour. When these data are compared to previous results in the rat, substantial differences are seen. As there are differences between the effects on rat and rabbit sexual behaviour by other types of drugs, it appears that drug action on sexual behaviour cannot be generalized from one species to another.

The role of subtypes of the opioid receptor in the anxiolytic action of chlordiazepoxide.

Previous studies have shown that the opiate antagonist naloxone blocks the anxiolytic-like effects of benzodiazepines in several models of anxiety, including the elevated plus-maze. Although naloxone preferentially binds to the mu opioid receptor, its selectivity is rather low. The opioid receptor subtype important for anxiolytic-like actions of benzodiazepines in the plus-maze remains, therefore, unknown. In the present experiments, the ability of antagonists selective for subtypes of the opioid receptor to block the anxiolytic-like effects of chlordiazepoxide in the elevated plus-maze was evaluated in Swiss mice. Chlordiazepoxide, 5 mg/kg, increased the proportion as well as the number of open arms entries without modifying closed arms entries. Lower doses of the benzodiazepine were ineffective. The mu receptor antagonist beta-funaltrexamine, 10 and 20 mg/kg, the delta antagonist naltrindole, 10 mg/kg, and the kappa antagonist nor-binaltorphimine, 2.5 and 5 mg/kg, were then combined with chlordiazepoxide, 5 mg/kg. beta-funaltrexamine, 10 mg/kg, reduced the effects of the benzodiazepine while the dose of 20 mg/kg completely blocked the effects. Nor-binaltorphimine was ineffective at a dose of 2.5 mg/kg, but completely inhibited the actions of chlordiazepoxide when the dose was 5 mg/kg. Naltrindole was ineffective. None of the antagonists affected plus-maze behavior when administered alone. It was concluded that the mu and kappa receptors are important for the anxiolytic-like actions of chlordiazepoxide in the elevated plus maze.

Intraaccumbens injections of substance P, morphine and amphetamine: effects on conditioned place preference and behavioral activity.

The nucleus accumbens of the rat plays a critical role in behavioral activation and appetitive motivation. Within the nucleus accumbens, the shell subarea may be especially relevant, since this site is anatomically related to other brain areas that are considered to play a critical role in the processing of motivation. We investigated the behavioral effects of local drug treatments aimed at the shell of the nucleus accumbens and tested the indirect dopamine agonist d-amphetamine, the opiate agonist morphine, and the neurokinin substance P. These substances are known to exert positive reinforcing effects, and can affect behavioral activity; effects that are physiologically closely related to the nucleus accumbens and its inputs and outputs. Our results show that unilateral microinjections of amphetamine (1.0 microg, 10.0 microg) into the shell of the nucleus accumbens dose-dependently stimulated behavioral activity (locomotion, rears, sniffing), and led to conditioned place preference. Furthermore, the effect of amphetamine on place preference was negatively related to the psychomotor stimulant action on rears. Morphine injections (5.0 microg) also stimulated behavioral activity and elicited contraversive turning, but were ineffective with respect to place preference. Finally, the neuropeptide substance P, injected in a dose range of 0.1-10.0 ng, had no significant behavioral effects. These findings are discussed with respect to the role of dopaminergic, peptidergic and cholinergic mechanisms in the nucleus accumbens. It is suggested that dopamine, opiates, and neurokinins in the shell of the nucleus accumbens are differentially involved in mediating behavioral activity and appetitive motivation.

Interactions between dopamine and GABA in the control of ambulatory activity and neophobia in the mouse.

Ambulatory activity in a familiar and novel environment as well as the time spent in a novel environment were evaluated using the free exploratory paradigm. Male mice treated with D-amphetamine, 2 mg/kg, displayed enhanced ambulatory activity in the familiar environment. The time spent in the novel environment was reduced by amphetamine, 1 and 2 mg/kg. The GABA transaminase inhibitor gamma-acetylen GABA (GAG) reduced ambulatory activity and rearing as well as the time spent in the novel environment. The mixed GABA(A)/GABA(B) agonist progabide, 200 mg/kg, reduced rearing both in the familiar and novel environments without affecting the time spent in the novel environment. Amphetamine, 1 mg/kg, was then combined with ineffective doses of GAG and progabide (50 and 100 mg/kg, respectively). The GABAergics did not reliably modify the effects of amphetamine on the time spent in the novel environment. Ambulatory activity and rearing were reduced both in comparison to amphetamine + saline and to control. These data show that GABAergic drugs are potentiated by enhanced dopaminergic neurotransmission with regard to their actions on ambulatory activity and rearing. The effects of progabide + amphetamine were then evaluated after treatment with the GABA(A) antagonist bicuculline or the GABA(B) antagonist CGP 35348. Neither bicuculline, 1 mg/kg, nor CGP 35348, 100 mg/kg, blocked the actions of progabide. The combined treatment with both antagonists was also unable to reduce the effects of progabide. These data suggest that the interaction between amphetamine and progabide with regard to motor effects depends on a non-GABA(A), non-GABA(B) receptor.

GABAergic drugs and socio-sexual behavior.

To elucidate the role of GABA in the control of sexual behavior, the effects of the GABA(A) agonist 4,5,6,7-tetrahydroisoxazolo[5,4c]-pyridin-3-ol (THIP), the GABA transaminase inhibitors sodium valproate and gamma-acetylen-GABA (GAG), and the GABA synthesis inhibitors isoniazide and deoxypyridoxine were evaluated in sexual behavior, exploration, and sociosexual interactions with a receptive female or a castrated male. Furthermore, to discriminate possible general inhibitory effects from those specific to sexual behavior, the doses of the drugs that produced a significant inhibition of copulation were tested in a free drinking procedure. THIP (16 mg/kg), sodium valproate (400 mg/kg), GAG (100 mg/kg), and deoxypyridoxine (400 mg/kg) produced a strong inhibition of sexual behavior. The percentage of animals displaying mounts and intromissions as well as the mean number of mounts and intromissions were significantly reduced. Sociosexual interactions with a receptive female or a castrated male and exploratory behaviors were also reduced. The most consistent effects observed were reductions in sniffing, self-grooming, and rearing. Drinking behavior was significantly reduced in doses that inhibited sexual behavior. These results further support the hypothesis that altered GABAergic neurotransmission produces reduced sensitivity to environmental stimuli and thereby inhibits sexual and drinking behavior in a nonspecific way.