Dopamine-dependent inhibition of glycine release in the rat nucleus accumbens during feeding

Food intake decreased the glycine extracellular level in the rat n.accumbens. Tetrodotoxin prevented the decrease, whereas D,L-threo-beta-hydroxyaspartic acid exerted no effect. Raclopride (D2 dopamine receptor antagonist) increased the glycine extracellular level in food intake. The data obtained suggest that during feeding the glycine release in the n.accumbens is controlled by the D2 dopamine receptors.     

Mediolateral gradient of the nucleus accumbens nitrergic activation during exploratory behavior

In Sprague-Dawley rats, by means of in vivo microdialysis combined with HPLC analysis it has been shown that an exploratory behavior in a new environment is accompanied by a rise in extracellular levels of citrulline (an NO co-product) in the mediolateral regions of the n. accumbens with the maximum observed in the medial n. accumbens. Infusions of 7-nitroindazole (0.5 mM), a neuronal NO synthase inhibitor, into the medial n. accumbens prevented the exploration-induced rise of extracellular citrulline levels in this area. The second presentation of the same chamber did not produce any significant changes of extracellular citrulline levels in the medial n. accumbens, although there was a tendency of a small increase. The presentation of a familiar chamber did not affect citrulline extracellular levels in this area. The data obtained indicate for the first time that exploratory activity in a new environment is accompanied by the nitrergic activation in the entire n. accumbens with the maximal activation in the medial part of this brain area.     

Comparison in changes of glutamate level in the rat nucleus accumbens induced by D1- and D2-dopamine receptors during feeding

The influence of dopamine D1- and D2-like receptors blockage on glutamate level in the n. accumbens of Sprague-Dawly rats during feeding was investigated by in vivo microdialysis combined with HPLC-EC analysis. Food intake resulted in a decrease in extracellular glutamate level. Infusion of D1-like dopamine receptor-blocker (SCH-23390, 0.01 mM) into the n. accumbens did not change this effect. Infusion of D2-like dopamine receptor-blocker (raclopride, 0.1 mM) into the n. accumbens caused an increase in extracellular glutamate level during feeding. The findings suggest, that decrease in extracellular glutamate level in n. accumbens is caused by dopamine D2-like, but not D1-like receptors activation.     

Vesicular and nonvesicular glutamate release in the nucleus accumbens during a forced switch in behavioral strategy

By means of in vivo microdialysis combined with HPLC analysis, we have shown that glutamate extracellular level in the rat n. accumbens increases during a forced switch in behavioral strategy. When infused in the n. accumbens, a Na+ channel blocker tetrodotoxin (TTX, 1 microM) completely prevents this increase whereas a potent cystine/glutamate exchanger blocker (S)-4-carboxyphenylglycine ((S)-4-CPG, 5 microM) has no effect. In contrast, TT (1 microM), infused in the n. accumbens, fails to significantly alter basal level of extracellular glutamate in this region whereas (S)-4-CPG (5 microM) produced a significant decrease. Our data suggest that basal and factional glutamate releases in the n. accumbens are differently regulated. The source of basal glutamate release is a non-vesicular release via cystine/glutamate exchanger. Functional glutamate release observed during a forced switch in behavioral strategy derives from vesicular synaptic pool.     

Changes in glutamate release in the rat nucleus accumbens during food and pain reinforcement

In vivo microdialysis combined with HPLC-EC analysis was used to monitor extracellular glutamate in the n. accumbens of Sprague-Dawley rats during footshock and food delivery. The footshock presentation resulted in a delayed increase in extracellular glutamate level, whereas the food intake caused its decrease. The intra-accumbens infusion of glutamate reuptake blocker D,L-threo-beta-hydroxiaspartate (1 mM) completely prevented the food-induced decrease in glutamate level. The intra-accumbens infusion of sodium channel blocker tetrodotoxin (1 microM) led to an increase in glutamate extracellular level in the n. accumbens in response to food intake. The results suggest that the food-induced decrease in glutamate extracellular level in the n. accumbens occurs due to an enhancement of high-affinity glutamate uptake that is probably under the neuronal control during feeding.     

Cooperative neuronal activity of the n. accumbens and the frontal cortex in cats trained to choose stimuli of various value

It was shown that the two-way interaction between neurons of the frontal cortex and n. accumbens progressively increases, whereas their regularity simultaneously decreases with the rise in impulsiveness and drop in self-control in behavior. In case of the long-latency instrumental reactions, a control of the frontal cortex neurons by neurons of the n. accumbens weakens during presentation of conditioned stimuli only in "impulsive" animals, which is correlated with low network activity of the n. accumbens. Comparison of patterns of fronto-accumbal interactions during performance of the same type of activity revealed similar correlations in the neuronal pairs before and during presentation of conditioned stimuli, whereas different patterns corresponded to different types of activity.     

Blockade of FG 7142-Induced Increased Dopamine Utilization by the Glycine/NMDA Receptor Antagonist (+)-HA 966

Abstract: Systemic administration of the anxiogenic benzodiazepine inverse agonist FG 7142 has been shown to increase selectively dopamine utilization in the medial prefrontal cortex and the shell, but not core, subregion of the nucleus accumbens. In the present study, we examined the functional interaction between benzodiazepine and N -methyl- d -aspartate receptor influences on dopamine utilization in these areas. Male Sprague-Dawley rats were pretreated with the glycine receptor antagonist (+)-HA 966 (15 mg/kg, i.p.) or saline 15 min before FG 7142 (20 mg/kg, i.p.) or vehicle administration. Subjects were killed 30 min later and assayed for tissue concentrations of dopamine and its major metabolite 3,4-dihydroxyphenylacetic acid in the core and shell subdivisions of the nucleus accumbens and the medial prefrontal cortex. (+)-HA 966 administration blocked FG 7142-induced increased dopamine utilization in both the medial prefrontal cortex and the shell subdivision of the nucleus accumbens. Results are discussed in terms of N -methyl- d -aspartate receptor influences on the response of mesoaccumbal dopamine neurons to stress.     

Glutamatergic regulation of citrulline extracellular level in the nucleus accumbens during acquisition and expression of conditioned emotional response

In Spregue-Dawley rats, by means of in vivo microdialysis combined with HPLC analysis, it was shown that acquisition and expression of conditioned emotional response increased extracellular level of citrulline: a nitric oxide coproduct, in the nucleus accumbens. Intraaccumbal infusion of MK-801 (100 microM): an NMDA antagonist, markedly attenuated the increase in extracellular citrulline in the n. accumbens produced by acquisition of the response, and completely prevented its conditioned rise observed during expression of the response. The data obtained suggest that, during acquisition and expression of the conditioned emotional response, glutamatergic input to the n. accumbens might act via NMDA receptors to stimulate NO production within this brain area.     

Effect of apomorphine injection into the nucleus accumbens on the limb preference in manipulation movements in rats

The concentration of dophamine and its derivates is known to correlate with the degree of handedness in manipulative movements in rodents. In this work we studied a possibility to changing handedness in rats by injection of a dopamine agonist into the nucleus accumbens. Retrieving food from a horizontal tube was used to determine the limb preference (10 food retrievals by the preferred limb). Then apomorphine was injected into the n. accumbens ipsilateral to the preferred limb in the course of 7 days. The same volume of buffer solution was injected into the contralateral n. accumbens. Just after the last injection the limb preference was tested. It was shown that the chronic injection of the non-specific agonist of dophamine receptors significantly changed the limb preference.     

Medial-frontal cortex hypometabolism in chronic phencyclidine exposed rats assessed by high resolution magic angle spin 11.7 T proton magnetic resonance spectroscopy

BackgroundProton magnetic resonance spectroscopy (¹H-MRS) clinical studies of patients with schizophrenia document prefrontal N-acetylaspartate (NAA) reductions, suggesting an effect of the disease or of antipsychotic medications. We studied in the rat the effect of prolonged exposure to a low-dose of the NMDA glutamate receptor antagonist phencyclidine (PCP) on levels of NAA, glutamate and glutamine in several brain regions where metabolite reductions have been reported in chronically medicated patients with schizophrenia.MethodsTwo groups of ten rats each were treated with PCP (2.58 mg/kg/day) or vehicle and were sacrificed after 1 month treatment. Concentrations of neurochemicals were determined with high resolution magic angle (HR-MAS) ¹H-MRS at 11.7 T in ex vivo punch biopsies from the medial frontal and cingulate cortex, striatum, nucleus accumbens, amygdala and ventral hippocampus.ResultsPCP treatment reduced NAA, glutamate, glycine, aspartate, creatine, lactate and GABA in medial frontal cortex. In the nucleus accumbens, PCP reduced levels of NAA, aspartate and glycine; similarly aspartate and glycine were reduced in the striatum. Finally the amygdala and hippocampus had elevations in glutamine and choline, respectively.ConclusionsLow-dose PCP in rats models prefrontal NAA and glutamate reductions documented in chronically-ill schizophrenia patients. Chronic glutamate NMDA receptor blockade in rats replicates an endophenotype in schizophrenia and may contribute to the prefrontal hypometabolic state in schizophrenia.     

Inhibitory regulation of glutamate receptors in the frog motoneuron

The interaction of exogenously applied excitatory (glutamate and their agonists NMDA, AMPA, kainate) and inhibitory (glycine and GABA) amino acid effects was studied intracellularly in the motoneurones of the isolated frog spinal cord. During simultaneous glycine or GABA bath applications GLU-, AMPA-, KA- and NMDA-evoked responses were, respectively, decreased up to 45.8 +/- 2.9% (n = 12) and 67.8 +/- 3.9% (n = 16), 13.9 +/- 4.3% (n = 9) and 32.1 +/- 8.3% (n = 12), 36.8 +/- 8.2% (n = 7) and 48.0 +/- 11.8% (n = 6), 7.7 +/- 3.5% (n = 9) and 18.1 +/- 3.8% (n = 14) from the control. Sequential applications of EAA after glycine or GABA as well as the applications of EAA-agonist and glycine (GABA) mixture demonstrated similar results. The decrease of EAA-responses by glycine and GABA was abolished by selective GlyR antagonist strychnine (1 microM) and the selective GABAR antagonist SR95531 (gabazine, 20 MM), respectively. The data revealed differences in inhibitory effect of glycine and GABA on the excitation responses mediated by different types of glutamate receptors in the frog motoneurones: the predominant inhibitory effect of glycine and GABA on NMDA-responses and weak inhibitory effect on KA- and GLU-responses. Inhibitory effect of glycine was twice as much as that of GABA at the same concentration.     

The enhancement of glutamate release in the nucleus accumbens of rats with a destroyed hippocampal formation during an emotional conditioned response]

It was shown by means of in vivo microdialysis combined with HPLC/EC analysis that the exocytotoxic lesions of the hippocampal formation impaired the emotional conditioning and led to additional glutamate release in the n. accumbens during acquisition and performance of the conditioned response. Thus, it was shown that the disruption of glutamatergic synaptic transmission in the n. accumbens results in a compensatory increase in the volume glutamatergic transmission in this structure.     

Effect of fentanyl and morphine on local blood flow and tissue oxygen tension in cortical frontal-parietal area and nucleus accumbens in albino rats

The aim of this study was to examine effects of i.p. injected Fentanyl (0.005 mg/kg) and Morphine (1 mg/kg) on local cerebral blood flow (ICBF) and tissue pO2 level in frontal-parietal area of the cortex and nucleus accumbens of the rat's brain. Either fentanyl or morphine injection resulted in significant increase of local blood flow in the n.accumbens and its decrease in frontal-parietal area of cortex. Measurement of oxygen partial pressure revealed the opposite (to ICBF) changes: a decrease in n.accumbens and its increase in cortical area of the brain. Analysis of this data and electrical activity recorded from both said structures allow to conclude that they are conditioned by respective changes in functional-metabolic activity induced by intraperitoneal injection either fentanyl or morphine: its suppression in frontal-parietal area of the cortex and development of seizure-like activity in the n.accumbens.     

D1 dopamine receptors regulate citrulline extracellular level in the nucleus accumbens during expression of conditioned fear response

In rats, expression of conditioned fear response increased extracellular level of citrulline in the nucleus accumbens. Infusion of SCH-23390 into the nucleus accumbens exerted no long-term effect on the baseline citrulline level but attenuated the increase in the extracellar citrulline produced by the expression of the response. The data obtained suggest that, during the expression of the conditioned fear response, the dopaminergic input to the n. accumbens might act via D1 receptors to stimulate NO production within this brain area.     

Effects of simultaneous dopamine- and glutamatergic stimulation of the n. accumbens on synaptic dopamine release in the striatum of free-ranging rats

Research was performed on free-ranging Sprague-Dawley strain rats using in vivo intracranial dialysis techniques combined with radioenzymatic analysis of dopamine level. Dialysis infusion of the n. accumbens with artificial cerebrospinal fluid containing a mixture of amphetamine and glutamate (each at a concentration of 10^–3 M) was found to intensify synaptic dopamine release into the dorsal striatum, while administering these substances separately to the n. accumbens induces inhibition of synaptic dopamine release in this striatal area. Findings indicate that the n. accumbens exerts an influence on function of the nigrostriatal dopaminergic system and that the pattern of this influence may be determined by interaction between dopamine- and glutamatergic inputs from this nucleus.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 22, No. 5, pp. 621–626, September–October, 1990.     

Incorporation of labelled glycine into reduced glutathione of intact human erythrocytes by enzyme-catalysed exchange. A nuclear-magnetic-resonance study.

1H, 2H and 15N n.m.r. spectroscopy was used to monitor the incorporation of free glycine into the glycine residue of reduced glutathione (GSH) in suspensions of intact human erythrocytes. The following results were obtained. (i) By using 1H spin-echo n.m.r. the exchange reaction between [2H5]glycine and the protonated glycine residue of GSH was studied at various [2H5]glycine concentrations, thus enabling the calculation of an apparent Michaelis constant (Km) and maximal velocity (Vmax.) for the process. (ii) The reaction is catalysed by glutathione synthetase and proceeds most rapidly in the absence of glucose, which is the main physiological energy source of the erythrocyte. (iii) 15N n.m.r. spectroscopy, with a one-pulse sequence, and 2H n.m.r. spectroscopy, with an inversion recovery method, enabled demonstration of the incorporation of labelled glycine into an intra-erythrocyte peptide, consistent with incorporation into GSH. (iv) The exchange reaction, although inhibited by glucose, appeared not to be dependent on low ATP or 2,3-bisphosphoglycerate concentrations.     

Citrulline extracellular level in the nucleus accumbens during acquisition and extinction of classical conditioned fear response with pain reinforcement

By means of in vivo microdialysis combined with HPLC analysis, we have shown that extracellular levels of citrulline (NO co-product) and arginine (NO precursor) increase in the rat n. accumbens during acquisition and expression of a classical fear response. The conditioned rise of citrulline and arginine levels gradually decreased in the course of extinction. The renewal of the response produced an increase in extracellular citrulline and arginine levels. These data suggest that the acquisition of conditioned fear response causes an increase in NO production in the n. accumbens that weakens during the extinction and is restored during the reinstatement of the response.     

Accumbens lesion in female rats increases mount rejection without modifying lordosis

Ovariectomized Wistar rats received bilateral electrolytic (n = 24) or sham (n = 11) lesion of the nucleus accumbens. Following priming with estradiol benzoate (25 micrograms/rat) and progesterone (0.5 mg/rat) they were tested for sexual behavior with a stud male. Tests were carried out once prior to operation and twice postoperatively. Both lordosis and rejection behaviors as responses to male mount attempts were evaluated for each session. Proceptive patterns (hopping, darting and presenting) were also recorded. Females with accumbens lesion did not differ from control animals either with regard to lordosis or to soliciting behaviors. On the contrary, the lesioned group showed a statistically significant increase in rejection behavior in both postoperative sessions (p less than 0.05 and p less than 0.002). In conclusion, nucleus accumbens lesion dissociated the normal correlation between lordosis and rejection responses to male mount attempts without affecting soliciting behaviors. This finding is thought to be related to the hyperreactivity produced by nucleus accumbens lesion.     

Tolerance to tyrosine hydroxylase activation in n. accumbens and c. striatum after repeated injections of "classical" and "atypical" antischizophrenic drugs.

Tolerance to the kinetic activation of tyrosine hydroxylase in both c. striatum and n. accumbens was produced as a result of chronic haloperidol treatment. Cross-tolerance to other “classical” antischizophrenic drugs was also observed. Chronic clozapine (an “atypical” antischizophrenic) failed to produce tolerance to the activation of TH in striatum and accumbens.     

β-alanine elevates dopamine levels in the rat nucleus accumbens: antagonism by strychnine

Glycine receptors (GlyRs) in the nucleus accumbens (nAc) have recently been suggested to be involved in the reinforcing and dopamine-elevating properties of ethanol via a neuronal circuitry involving the VTA. Apart from ethanol, both glycine and taurine have the ability to modulate dopamine output via GlyRs in the same brain region. In the present study, we wanted to explore whether yet another endogenous ligand for the GlyR, β-alanine, had similar effects. To this end, we monitored dopamine in the nAc by means of in vivo microdialysis and found that local perfusion of β-alanine increased dopamine output. In line with previous observations investigating ethanol, glycine and taurine, the competitive GlyR antagonist strychnine completely blocked the dopamine elevation. The present results suggest that β-alanine has the ability to modulate dopamine levels in the nAc via strychnine-sensitive GlyRs, and are consistent with previous studies suggesting the importance of this receptor for modulating dopamine output.