Dopamine In Nucleus Accumbens Septi Research Articles

Electrical Stimulation of the Prefrontal Cortex Increases Cholecystokinin, Glutamate, and Dopamine Release in the Nucleus Accumbens: anIn VivoMicrodialysis Study in Freely Moving Rats

In vivo microdialysis, radioimmunoassay, and HPLC with electrochemical or fluorometric detection were used to investigate the release of cholecystokinin (CCK), glutamate (Glu), and dopamine (DA) in nucleus accumbens septi (NAS) as a function of ipsilateral electrical stimulation of medial prefrontal cortex (mPFC). CCK was progressively elevated by mPFC stimulation at 50-200 Hz. Stimulation-induced CCK release was intensity-dependent at 250-700 microA. NAS Glu and DA levels were each elevated by stimulation at 25-400 Hz; the dopamine metabolites DOPAC and homovanillic acid were increased by stimulation at 100-400 Hz. When rats were trained to lever press for mPFC stimulation, the stimulation induced similar elevations of each of the three transmitters to those seen with experimenter-administered stimulation. Perfusion of 1 mM kynurenic acid (Kyn) into either the ventral tegmental area (VTA) or NAS blocked lever pressing for mPFC stimulation. VTA, but not NAS, perfusion of Kyn significantly attenuated the increases in NAS DA levels induced by mPFC stimulation. Kyn did not affect NAS CCK or Glu levels when perfused into either the VTA or NAS. The present results are consistent with histochemical evidence and provide the first in vivo evidence for the existence of a releasable pool of CCK in the NAS originating from the mPFC. Although dopamine is the transmitter most closely linked to reward function, it was CCK that showed frequency-dependent differences in release corresponding most closely to rewarding efficacy of the stimulation. Although not essential for the reward signal itself, coreleased CCK may modulate the impact of the glutamatergic action in this behavior.

Left and right 6-hydroxydopamine lesions of the medial prefrontal cortex differentially alter subcortical dopamine utilization and the behavioral response to stress

The effects of left and right prefrontal cortical dopamine (DA) depletion on circling behavior, stress-escape behavior and subcortical DA function were examined in rats exhibiting left or right turning biases. 6-Hydroxydopamine lesions of the medial prefrontal cortex (PFC) caused significant DA depletions when assessed in separate studies at 3 days and 3–4 weeks. However, depletions were smaller at 3–4 weeks and there was a significant increase in DA concentration on the left side following right lesions. Significant increases in striatal DA content were observed following lesions of either side at 3–4 weeks, but not at 3 days. No changes in DA concentration were observed in the nucleus accumbens septi (NAS). Left circling rats significantly increased their circling behavior following right sided lesions and showed disrupted footshock-escape behavior following left sided lesions. Performance of the footshock-escape task exerted an effect on striatal and NAS DA utilization as indicated by the ratio of 3,4-dihydroxyphenylacetic acid (DOPAC) to DA. The effects of footshock on NAS DA utilization were greater following left PFC lesions as compared to the right lesion and sham conditions. These lesion effects were also greater in left- than in right-turning animals. The data indicate that an intrinsic asymmetry in brain DA systems interacts with left and right PFC lesions to differentially determine subcortical DA function and behaviors that it subserves.

Conditioned place preference and locomotor activation produced by injection of psychostimulants into ventral pallidum

The ventral pallidum (VP) is often viewed as an output structure of the nucleus accumbens septi (NAS). However, VP, like NAS, receives a dopaminergic input from the ventral tegmental area. These experiments investigated some behavioral effects of microinjection into VP of drugs which enhance dopaminergic transmission. Injection of 25 μg dopamine or 5–10 μg amphetamine into VP produced hypermotility. In contrast, injection of 12.5–50 μg cocaine initially suppressed, then increased, activity. Injection of 100 μg cocaine only produced hypomotility in the 1-h period examined. The hypomotility following cocaine seemed to be a local anesthetic effect, because it was mimicked by 50–200 μg procaine. Procaine did not, however, produce subsequent hypermotility. Conditioned place preference (CPP) was produced by 10 μg amphetamine and 50 μg cocaine but not 100 μg procaine. We conclude that injection of cocaine into VP, unlike similar injections into NAS, produces CPP. These results support the idea of an involvement of dopamine in VP in reward and locomotor activation, independent of dopamine in NAS. The use of intracerebral injections of cocaine is complicated, however, by an apparent local anesthetic effect of the drug.

U-50,488H into A10 reduces haloperidol-induced elevations of accumbens dopamine.

Injections of kappa (k) opioid agonists into the A10 ventral tegmental area (VTA) induce behavioral inhibitions and decreased interest in incentive stimuli, behavioral changes indicative of decreased mesolimbic dopamine (DA) transmission. In seeming contrast, three separate laboratories have recently reported that intra-VTA injections of k agonists do not affect nucleus accumbens septi (NAS) basal levels of extracellular DA. In the present experiment, we investigated whether intra-VTA injections of a k agonist would decrease pharmacologically-stimulated increased levels of extracellular NAS DA. It was found that intra-VTA injections of the k agonist U-50,488H significantly attenuated haloperidol-induced elevations of DA, as measured by in vivo microdialysis.

Destruction of 5-hydroxytryptaminergic neurons and the dynamics of dopamine in nucleus accumbens septi and other forebrain regions of the rat

5,7-Dihydroxytryptamine (5,7-DHT) was injected into the lateral cerebral ventricle of rats which had been pretreated with desipramine; this treatment reduced the concentrations of 5-hydroxy-tryptamine (5-HT) but not of norepinephrine or dopamine (DA) in forebrain regions. When 5,7-DHT was injected bilaterally into the nucleus accumbens septi (NAS) of desipramine-pretreated rats, it selectively depleted 5-HT only from the NAS. Exploratory locomotor activity and the locomotor stimulation induced by f-amphetamine and apomorphine were enhanced in both NAS- and 5,7-DHT-injected rats. These locomotor effects in the 5-HT-depleted animals were not associated with changes in the activity of dopaminergic neurons, which were estimated biochemically from either the regional concentrations of dihydroxyphenylacetic acid (DOPAC) or the rate of accumulation of dihydroxyphenylalanine (DOPA) after the administration of a decarboxylase inhibitor. That is, the concentration of DOPAC and the accumulation of DOPA in the NAS, olfactory tubercle and striatum of NAS-5,7-DHT and 5,7-DHT-injected rats were the same as in controls. Furthermore, the ability of apomorphine to decrease, and of haloperidol to increase, DOPAC concentrations and DOPA accumulation were the same in control, NAS-5,7-DHT and 5,7-DHT-injected rats. These results indicate that the enhancement of spontaneous and drug-stimulated locomotor activity following destruction of 5-HT nerve terminals in the brain are not associated with changes in the activity of the major ascending DA-containing neuronal systems.