Mei-Yun Tai

Striatal glutamate release during novelty exposure-induced hyperactivity in olfactory bulbectomized rats

Striatal glutamate release during novelty exposure-induced hyperactivity was studied by microdialysis in freely-moving olfactory bulbectomized (OBX) rats. After collecting three 10 min basal striatal dialysate samples, the animals were transferred to an open-field apparatus (novelty) and locomotor activity recorded for 60 min. OBX rats showed significantly more locomotor activity (1210+/-270 cm) than sham-operated rats (420+/-70 cm), but only in the first 10 min after exposure to the novel environment. During the same period, striatal glutamate levels increased to 163+/-21% of the basal value in OBX rats, while no changes were seen in the striatum of sham-operated controls. These findings suggest that olfactory bulbectomy results in an increased response of the striatal glutamatergic system to novelty stress, and may consequently cause hyperactivity.

Dopamine release in the nucleus accumbens during sexual behavior in prenatally stressed adult male rats

In vivo microdialysis experiments were performed on the nucleus accumbens (NAc) during observation of sexual behavior (including motivation and copulation) to determine if there were any changes in NAc dopamine (DA) transmission in prenatally stressed (PS) adult male rats. Approximate 37% of control males and 83% of PS males did not exhibit copulation during the sexual behavior tests and no significant changes in NAc DA release were seen during exposure to estrous females. In contrast, both control and PS males that displayed copulatory behavior showed a marked increase in NAc DA release when presented with a sexually receptive female behind a screen and this increased further during actual copulation. The increase in DA release in copulatory PS males was not significantly different from that in sexually active control males. In addition, a similar extent in DA release induced by high potassium perfusate was observed in all rats. These results suggest that prenatal stress may result in a deficit in DA neurotransmission in the NAc and this deficit may possibly cause impaired male sexual behavior in rats.

Sexual motivation is demasculinized, but not feminized, in prenatally stressed male rats.

Sexual motivation and copulation in male rats are associated with dopamine release in the nucleus accumbens. Demasculinized copulatory behavior has been demonstrated in prenatally stressed adult male rats. We have previously reported that approximately 80% of prenatally stressed male rats do not exhibit copulation and that no significant changes in nucleus accumbens dopamine release are seen during exposure to estrous females. In the present study, we investigated whether prenatal stress affects sexual motivation in these animals as adults. Pregnant Wistar rats were subjected to immobilization stress for two hours daily from day 15-19 of gestation. The prenatally stressed male offspring at the age of 3 months were allowed contact with receptive female rats for a 30 min period per week for 10 weeks; then, between the age of 5 and 6 months, their sexual motivation and copulatory activity were measured. Sexual motivation was measured in terms of sexual partner preference. The number of visits and the duration of each visit to an estrous female (stimulus female) or to a sexually active male rat (stimulus male) were recorded. Compared with control males, prenatally stressed male rats showed a significantly lower number of visits and a shorter duration of each visit to stimulus females. Prenatally stressed males showed no preference for male or female stimulus rats in terms of the number of visits and the duration of each visit, whereas control rats showed a significantly higher number of visits and duration of visits to female stimulus rats than male stimulus rats. A significant decrease in copulatory activity was observed in the prenatally stressed male offspring compared with control male rats, with most of the prenatally stressed males failing to show copulation. In vivo microdialysis experiments were performed on the nucleus accumbens with concurrent observation of sexual behavior. The prenatally stressed rats that did not exhibit copulation showed no significant changes in nucleus accumbens dopamine release during exposure to a stimulus male behind a wire-mesh barrier and the amount of dopamine release remained at the basal levels during actual physical contact. These results, combined with those of our previous report, indicate that sexual motivation in prenatally stressed male rats is demasculinized, but not feminized.

Effects of olfactory bulbectomy on NMDA receptor density in the rat brain: [3H] MK-801 binding assay

Olfactory bulbectomy (OBX) transects the glutamatergic efferents from the olfactory bulbs, and the changes of glutamatergic N-methyl-D-aspartate (NMDA) receptor-mediated function are though to be involved in the behavioral deficits seen in OBX rats. In the present study, irritability scores in OBX male Wistar rats were correlated with discrete regional effects on NMDA receptor function measured using a [3H] MK-801 binding assay. Irritability scores, measured before and for 2 weeks after OBX, showed a gradual increase in irritability after OBX. A reduction of the NMDA receptor density was observed in the cerebral cortex and amygdala 16 days after OBX, but not in the striatum, olfactory tubercle, entorhinal cortex, and hippocampus. These results demonstrate that OBX causes changes in the NMDA receptor system in certain brain regions and suggest that these changes may be responsible for the behavioral deficits of OBX rats.

Monoamine levels in the nucleus accumbens correlate with male sexual behavior in middle-aged rats.

The correlation between monoamine levels in the nucleus accumbens (NAcc) and male sexual behavior was studied in middle-aged rats. Male rats (18-19months) were assigned to three groups: (1) Group MIE consisted of rats showing mounts, intromissions, and ejaculations; (2) Group MI was composed of rats showing mounts and intromissions, but no ejaculation; and (3) Group NC were non-copulators showing no sexual behavior. Young adult rats (4-5months), displaying complete copulatory behavior, were used as the control group. Levels of dopamine (DA), serotonin, and norepinephrine and their metabolites in the NAcc were measured by high-pressure liquid chromatography with electrochemical detection. No difference was seen in DA levels between MIE rats and young controls, whereas DA levels in NC rats were significantly lower than those in both MIE and MI rats. Serotonin levels in NC rats were significantly higher than those in MIE and MI rats. Conversely, norepinephrine levels in NC rats were lower than those in MIE rats. These results suggest that monoamine levels in the NAcc correlate with sexual performance in male rats and that changes in NAcc monoamine levels might affect male sexual behavior in middle-aged rats.

Male sexual behavior and catecholamine levels in the medial preoptic area and arcuate nucleus in middle-aged rats.

The correlation between male sexual behavior and catecholamine levels in the medial preoptic area (MPOA) and arcuate nucleus (ARN) was studied in middle-aged rats. Male rats (18-19 months) were assigned to three groups: (1) Group MIE, consisting of rats showing mounts, intromissions, and ejaculations; (2) Group MI, consisting of rats showing mounts and intromissions, but no ejaculation; and (3) Group NC, consisting of non-copulators showing no sexual behavior. Young adult rats (4-5 months) displaying complete copulatory behavior were used as the control group. Dopamine (DA) and norepinephrine (NE) tissue levels in the MPOA and ARN were measured by high pressure liquid chromatography with electrochemical detection. There were no differences between MIE rats and young controls in DA or NE tissue levels in these two brain areas. Furthermore, no differences were found between the MI and NC groups in DA or NE tissue levels in either the MPOA or ARN. DA tissue levels in the MPOA and ARN in the MI and NC groups were significantly lower than those in the MIE group. NE tissue levels in the MPOA of the NC group were significantly lower than those in the MIE group, but no differences in NE tissue levels in the ARN were seen between the four groups. These results suggest that, in male rats, complete male sexual performance is related to tissue levels of DA, but not of NE, in the MPOA and/or ARN. Furthermore, ejaculatory behavior might be associated with critical DA tissue levels in the MPOA and/or ARN in middle-aged rats.

MK-801 suppresses muricidal behavior but not locomotion in olfactory bulbectomized rats: involvement of NMDA receptors

In rats, olfactory bulbectomy (OBX) causes changes in glutamatergic function in the amygdala (AMG) and induces mouse-killing behavior (MKB). The medial AMG (mAMG) plays an important role in the initiation and maintenance of OBX-induced MKB. In the present study, systemic injection or intra-mAMG perfusion of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801) was used to determine the effects of MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, on the expression of OBX-induced MKB in male Wistar rats that had undergone OBX 1 month previously. The effects of MK-801 on locomotion in OBX rats were also examined using the open-field test. Intraperitoneal injection of MK-801 at doses of 0.10 and 0.15 mg/kg resulted in reversible suppression of MKB, the effect being maximal within 1 h after drug treatment, then gradually disappearing over 6 h. Locomotor distance in OBX rats was not affected using 0.10 mg/kg of MK-801, but increased after treatment with 0.15 mg/kg of MK-801; both doses, however, caused the rats to spend longer in the central area of the open field. MKB was also reversibly suppressed by local perfusion of 1 mM MK-801 at a rate of 1 microl/min into the mAMG through microdialysis probes. These results suggest that NMDA receptors, at least, in the mAMG, are involved in the expression of OBX-induced MKB.

Effects of age on dopamine release in the nucleus accumbens and amphetamine-induced locomotor activity in rats

The effects of age on dopamine (DA) release in the nucleus accumbens (NAc) and on amphetamine (AMPH)-induced locomotor activity were studied by microdialysis in freely-moving young (5 month) and old (24 month) rats. Both basal extracellular DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release and that following intra-accumbens perfusion of AMPH (1-10 microM) were significantly lower in old rats. After intraperitoneal injection of AMPH (1.5 mg/kg), no age-related change in DA release was seen in the NAc, but locomotor activity was found to increase much more in young rats than in old ones. These results indicate that (1) old rats show decreased extracellular DA and DOPAC release, both in the basal state and following intra-accumbens infusion of AMPH, and (2) the age-related locomotor activity induced by systemic injection of AMPH is not paralleled by changes in DA release in the NAc.

Differential involvement of medial prefrontal cortex and basolateral amygdala extracellular signal-regulated kinase in extinction of conditioned taste aversion is dependent on different intervals of extinction following conditioning.

Extinction reflects a decrease in the conditioned response (CR) following non-reinforcement of a conditioned stimulus. Behavioral evidence indicates that extinction involves an inhibitory learning mechanism in which the extinguished CR reappears with presentation of an unconditioned stimulus. However, recent studies on fear conditioning suggest that extinction erases the original conditioning if the time interval between fear acquisition and extinction is short. The present study examined the effects of different intervals between acquisition and extinction of the original memory in conditioned taste aversion (CTA). Male Long-Evans rats acquired CTA by associating a 0.2% sucrose solution with malaise induced by i.p. injection of 4 ml/kg 0.15 M LiCl. Two different time intervals, 5 and 24 h, between CTA acquisition and extinction were used. Five or 24 h after CTA acquisition, extinction trials were performed, in which a bottle containing 20 ml of a 0.2% sucrose solution was provided for 10 min without subsequent LiCl injection. If sucrose consumption during the extinction trials was greater than the average water consumption, then rats were considered to have reached CTA extinction. Rats subjected to extinction trials lasting 24 h, but not 5 h, after acquisition re-exhibited the extinguished CR following injection of 0.15 M LiCl alone 7 days after acquisition. Extracellular signal-regulated kinase (ERK) in the medial prefrontal cortex (mPFC) and basolateral nucleus of the amygdala (BLA) was examined by Western blot after the first extinction trial. ERK activation in the mPFC was induced after the extinction trial beginning 5 h after acquisition, whereas the extinction trial performed 24 h after acquisition induced ERK activation in the BLA. These data suggest that the original conditioning can be inhibited or retained by CTA extinction depending on the time interval between acquisition and extinction and that the ERK transduction pathway in the mPFC and BLA is differentially involved in these processes.

Male sexual behavior is associated with LHRH neuron number in middle-aged rats

LHRH administration is reported to facilitate male sexual behavior. The aim of the present study was to investigate whether male sexual behavior is associated with the number of LHRH neurons in the forebrain in middle-aged rats. Male Long-Evans rats (18-19 months) were assigned to three groups on the basis of sexual performance: (1) group MEI consisted of rats showing complete copulatory patterns, including mounts, intromissions and ejaculations, (2) group MI was composed of rats showing mounts and intromissions, but no ejaculation and (3) group NC were non-copulators, i.e. they did not show any copulatory behavior. Young adult rats (4-5 months), displaying sexual behavior, were used as controls. Following the sexual behavior tests, the number of LHRH neurons in the medial septum (MS), organum vasculosum of the lamina terminalis (OVLT), preoptic area (POA) and anterior hypothalamus (AH) was determined by immunocytochemistry. No difference was seen in the total number of LHRH neurons in these combined brain areas between group MIE and young controls. In the three middle-aged groups, the total number of LHRH neurons was greatest in group MIE, less in group MI, and lowest in group NC. In general, a similar trend was seen separately in the MS, OVLT and POA. These results suggest that changes in the number of LHRH neurons in the forebrain, in most cases, are age-related, at least in the middle-aged rats, but they also seem to be associated with male sexual performance.