Hideyasu Yokoo

Psychological stress increases serotonin release in the rat amygdala and prefrontal cortex assessed by in vivo microdialysis

The effects of psychological stress on serotonin (5-HT) release were studied in the basolateral amygdaloid nucleus and the prefrontal cortex in conscious rats with in vivo microdialysis. Psychological stress, wherein emotional factors were predominantly involved, significantly increased extracellular 5-HT levels in these two areas. These findings suggest that activation of serotonergic neurons in these brain regions is involved in the emotional and/or cognitive states in animals.

Eating and drinking cause increased dopamine release in the nucleus accumbens and ventral tegmental area in the rat : measurement by in vivo microdialysis

Dopamine (DA) release was simultaneously monitored in the nucleus accumbens (NAC) and ventral tegmental area (VTA) of conscious rats using in vivo microdialysis. During dialysis perfusion, rats were allowed access to food or water for 20 min following a 36 h food and water deprivation period. DA release increased significantly in the NAC and VTA in response to eating and drinking. The increases in both regions continued until 20-60 min after the end of the feeding or drinking session. These results show that the mesolimbic DA pathway is activated in response to ingestive behavior, and that DA release occurs in the cell body (A10) region as well as in the mesolimbic DA nerve terminals.

Psychological stress increases dopamine turnover selectively in mesoprefrontal dopamine neurons of rats: reversal by diazepam.

The effects of psychological stress on catecholamine and indoleamine metabolism were examined in various brain regions of rats. Psychologically stressed rats were exposed to emotional responses of foot-shocked rats, but were themselves prevented from receiving foot-shock. Psychological stress for 30 min resulted in significant increases of both 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in the medial prefrontal cortex (MPFC), but not in other dopamine (DA) terminal fields. The levels of noradrenaline (NA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were unaffected in all brain regions examined after 30 min of psychological stress. A small but significant increase of DOPAC levels in the ventral tegmental area (VTA) was observed after a shorter (10 min) duration of stress. Moreover, an increase of DOPAC levels in the MPFC 30 min after psychological stress was attenuated by diazepam (5 mg/kg), and this attenuating effect was antagonized by Ro 15-1788 (15 mg/kg). These results suggest that mesoprefrontal DA neurons are selectively activated by psychological stress, and that the activation of the A10 cell body site (VTA) may precede that of the terminal field (MPFC). Moreover, diazepam was found to possess an inhibitory effect on the activation of mesoprefrontal DA neurons induced by psychological stress, and this effect may be partly mediated by benzodiazepine (BZD) receptors and implicated in the specific anxiolytic action of BZDs.

Noradrenaline release in the rat amygdala is increased by stress : studies with intracerebral microdialysis

The effects of immobilization and tail-pinch stress on extracellular noradrenaline (NA) release in the amygdala were studied in freely moving rats with intracerebral microdialysis techniques. After collection of basal levels of NA (2.63 +/- 0.26 pg/50 microliters/20 min), the rat was exposed to either immobilization stress or tail-pinch stress for 20 min. Immobilization and tail-pinch stress increased NA release to 250 and 243% of basal levels, respectively and the elevation of NA release was observed for 60 min and 40 min after release from stress, also respectively. These data suggest that microdialysis is a useful way to study extracellular NA release in the amygdala and that NA neurons in this region are activated by both immobilization and tail-pinch stress.

Opposite changes in the mesolimbic dopamine metabolism in the nerve terminal and cell body sites induced by locally infused baclofen in the rat

Infusion of baclofen (10(-4) M, 1 h) into the ventral tegmental area (VTA), the cell body site of mesolimbic dopamine (DA) neuron system in conscious rats, caused a decrease in both axonal and somatodendritic DA release in this neuron system, when monitored by in vivo microdialysis using two probes simultaneously placed in both the NAC and the VTA. Levels of the metabolite of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) in the VTA decreased significantly in a similar manner following infused baclofen into the VTA, however, a pronounced increase in DOPAC outflow was observed in dialysates from the NAC. This dissociated changes in DA metabolism observed in the NAC may possibly be derived from regulatory mechanisms via an autoreceptor located in the DA nerve terminals.

Direct evidence of conditioned fear-elicited enhancement of noradrenaline release in the rat hypothalamus assessed by intracranial microdialysis

Inescapable footshock stress produced marked increases in noradrenaline (NA) release, which was assessed by intracranial microdialysis, in the hypothalamus of conscious rats. Emotional stress, without physical stimuli (replacement to the environment where the rats had received footshock previously), also increased hypothalamic NA release. These results suggest that foodshock stress caused increases in NA release and this activation of NA neurons appears to be reinstated simply by re-exposure to the environment previously associated with shock.

Facilitatory modulation of mesolimbic dopamine neuronal activity by a μ-opioid agonist and nicotine as examined with in vivo microdialysis

Administration of either Tyr-D-Ala-Gly-MePhe-Gly(ol) (DAGO), a mu-opioid agonist, or nicotine into the VTA (A10) caused an increase in both dopamine (DA) and its metabolite levels in both the A10 region and DA nerve terminals in the nucleus accumbens of rats when assessed with dual probe brain dialysis. These findings show that DAGO and nicotine increase both axonal- and somatodendritic-DA release, as well as metabolic activity in mesolimbic DA neurons, possibly by inducing an increase in neuronal impulse flow.

Amantadine increases the extracellular dopamine levels in the striatum by re-uptake inhibition and by N-methyl-D-aspartate antagonism.

This study was performed to investigate the mechanism how amantadine increases the extracellular dopamine (DA) levels in the striatum in vivo. Local application of amantadine (1 mM, 40 min) to the striatum through the dialysis membrane significantly increased the extracellular DA levels. Coadministration of nomifensine (10 mM, 120 min), an inhibitor of neuronal DA uptake, into the perfusion fluid attenuated the amantadine-induced increase in DA outflow. The amantadine-induced increases in the extracellular DA levels were also inhibited by co-perfusion with Ringer containing high Mg2+ (15 mM, 120 min) or with MK-801 (1 microM, 80 min). These findings suggest that amantadine increases the extracellular DA levels in the striatum by inhibiting the re-uptake of DA and/or by blocking the channel in the N-methyl-D-aspartate (NMDA) receptor, which results in antagonism of NMDA receptor function.

Expression of aggression attenuates both stress-induced gastric ulcer formation and increases in noradrenaline release in the rat amygdala assessed by intracerebral microdialysis

The effects of an aggressive biting response on stress-induced noradrenaline (NA) release in the rat amygdala and gastric ulcer formation were studied with an intracerebral microdialysis technique. Rats were exposed to a 60-min period of cold restraint stress with or without being allowed to bite a wooden stick. They were sacrificed 100 min after release from stress to investigate gastric ulcer formation. Cold-restraint stress increased NA release to 304 +/- 22.3 and 206 +/- 23.8% of basal levels (mean +/- SEM) in the nonbiting and biting groups, respectively. The stress-induced increases in NA release in the nonbiting group were significantly higher than those in the biting group. In the nonbiting group, significant increases in NA release continued for 80 min after release from stress; however, NA levels in the biting group recovered to basal levels immediately after the cessation of stress. Although many severe gastric lesions with bleeding were found in the nonbiting group, fewer gastric lesions without bleeding were found in the biting group. The cumulative length of gastric lesions in the nonbiting group and in the biting group was 26.2 +/- 7.4 and 6.8 +/- 3.9 mm (mean +/- SEM), respectively. The mean number of ulcers in the nonbiting group and the biting group was 11.8 +/- 1.3 and 1.8 +/- 0.7 (mean +/- SEM), respectively. Both the cumulative length of ulcers and the number of ulcers were significantly lower than those seen in the nonbiting group. These findings strongly suggest that expression of aggression during stress exposure attenuates not only stress-induced increases in NA release in the rat amygdala but also gastric ulcer formation consequent to stress.

Stress-induced increase in noradrenaline release in the rat hypothalamus assessed by intracranial microdialysis

The hypothalamic microdialysis of conscious rats was used to investigate the effects of immobilization stress (20 min) on extracellular noradrenaline(NA) levels. The stress significantly increased NA levels relative to basal efflux by 106% and this elevation continued for 40 min after release from stress.