Katsuhiro Mizoguchi

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.

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.

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.

PSYCHOLOGICAL STRESS-INDUCED INCREASES IN NORADRENALINE RELEASE IN RAT BRAIN REGIONS ARE ATTENUATED BY DIAZEPAM, BUT NOT BY MORPHINE

By measuring levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4) in the hypothalamus, amygdala and locus coeruleus region, we investigated the effects of diazepam 5.0 mg/kg, morphine 6.0 mg/kg, or naloxone at 5.0 or 10 mg/kg injected SC immediately before stress exposure, on increases in NA release caused by psychological stress. Psychological stress, wherein rats were exposed to emotional responses which were displayed by other electrically shocked rats, significantly increased MHPG-SO4 levels in the three brain regions examined and elevated plasma corticosterone levels. Both increases in brain MHPG-SO4 levels and elevations of plasma corticosterone levels induced by stress were attenuated significantly by diazepam but neither by morphine nor by naloxone. MHPG-SO4 levels in the hypothalamus and amygdala in the morphine-stress group were significantly higher than those in the saline-stress group. These findings suggest that psychological stress, in which an emotional factor is predominantly involved, causes increases in NA release in these brain regions examined and that these increases are attenuated only by diazepam, in contrast to the previous report, where increases in brain NA release caused by immobilization stress are attenuated not only by diazepam but also by morphine and are enhanced by naloxone.

Effect of opioid peptides on dopamine release from nucleus accumbens after repeated treatment with methamphetamine

The effect of opioid peptides on extracellular dopamine levels in the nucleus accumbens was compared between rats treated with methamphetamine and saline repeatedly (for 9 days) by using microdialysis. After the period of repeated treatment, the rats in both groups were kept for an additional 9 days without further treatment. Repeated administration of methamphetamine reduced the decreasing effect of dynorphin (10 microM), applied locally in the perfusate, and enhanced the increasing effect of [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, 10 microM) on the extracellular dopamine levels in the nucleus accumbens. It is possible that repeated treatment with methamphetamine leads to attenuation of the inhibition and enhancement of the stimulation of dopamine release from the nucleus accumbens via presynaptic dynorphin- and enkephalin-sensitive receptors, respectively.

The role of ATP-sensitive potassium channels in striatal dopamine release: An in vivo microdialysis study

We used in vivo brain microdialysis to investigate the role of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in dopamine (DA) release regulated by DA autoreceptors in the rat striatum. Local infusions of the KATP channel opener nicorandil (10(-5)-10(-3) M) into the striatum through the dialysis membrane produced dose-dependent decreases in extracellular concentrations of DA. Local application of the D2 receptor antagonist (-)-sulpiride (SLP, 10(-5) M) or the KATP channel blocker quinine (QIN, 10(-3) M) produced significant increases in extracellular concentrations of DA. Nicorandil (10(-3) M) significantly blocked SLP (10(-5) M)- or QIN (10(-3) M)-induced increases in DA levels in the striatum. These results suggest that activation or inhibition of the KATP channel in the striatum causes decreases or increases, respectively, in endogenous DA release in vivo. Furthermore, SLP-induced increases in DA levels caused by blocking the tonic activation of DA autoreceptors are inhibited by the activation of KATP channels. These data suggest that striatal DA autoreceptors may inhibit DA release tonically by activating the KATP channel.

ATP-sensitive K+ channel openers block sulpiride-induced dopamine release in the rat striatum

In vivo brain microdialysis was used to investigate the role of ATP-sensitive K+ (KATP) channel openers in dopamine release regulated by dopamine autoreceptors in the rat striatum. Local infusion of two KATP channel openers, nicorandil (10(-5)-10(-3) M) and cromakalim (10(-5)-10(-3) M), into the striatum thorough the dialysis membrane produced dose-dependent decreases in extracellular concentrations of dopamine. Local application of the dopamine D2 receptor antagonist, (-)-sulpiride (10(-5) M), produced significant increases in extracellular concentrations of dopamine. Both nicrorandil (10(-5) M) and cromakalim (10(-4) M) blocked significantly (-)-sulpiride (10(-5) M)-induced increases in dopamine levels in the striatum. These results suggest that activation of KATP channels in the striatum causes decreases in endogenous dopamine release in vivo. Furthermore, the sulpiride-induced increases in dopamine levels caused by blocking the tonic activation of dopamine autoreceptors were inhibited by activation of KATP channel. These data indicate that KATP channels may be present in nigrostriatal dopaminergic terminals and that striatal dopamine autoreceptors inhibit dopamine release tonically by activation of KATP channels.

Differential changes in rat brain noradrenaline turnover produced by continuous and intermittent restraint stress

This experiment was performed to investigate differential effects of continuous and intermittent restraint stress on noradrenaline (NA) turnover in brain regions of male Wistar rats by measuring levels of a major metabolite of NA, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4) levels, as well as by measuring levels of plasma corticosterone and organ weights of the thymus, spleen, and adrenal glands. Rats in the 15-min and 30-min intermittently stressed groups showed significantly larger increases in MHPG-SO4 levels in most brain regions relative to those in the 90-min and 180-min continuously stressed groups, even though the total stress duration was equal or shorter. Body weight loss and loss of relative thymus weight in the 15-min intermittently stressed groups were the most marked among the five treatment groups. These findings suggest that stress-rest cyclicity is critical in determining the extent of stress-induced brain NA turnover and peripheral physiological responses.