Pallidal Dopamine Research Articles

Dopaminergic control of the globus pallidus through activation of D2 receptors and its impact on the electrical activity of subthalamic nucleus and substantia nigra reticulata neurons.

The globus pallidus (GP) receives dopaminergic afferents from the pars compacta of substantia nigra and several studies suggested that dopamine exerts its action in the GP through presynaptic D2 receptors (D2Rs). However, the impact of dopamine in GP on the pallido-subthalamic and pallido-nigral neurotransmission is not known. Here, we investigated the role of dopamine, through activation of D2Rs, in the modulation of GP neuronal activity and its impact on the electrical activity of subthalamic nucleus (STN) and substantia nigra reticulata (SNr) neurons. Extracellular recordings combined with local intracerebral microinjection of drugs were done in male Sprague-Dawley rats under urethane anesthesia. We showed that dopamine, when injected locally, increased the firing rate of the majority of neurons in the GP. This increase of the firing rate was mimicked by quinpirole, a D2R agonist, and prevented by sulpiride, a D2R antagonist. In parallel, the injection of dopamine, as well as quinpirole, in the GP reduced the firing rate of majority of STN and SNr neurons. However, neither dopamine nor quinpirole changed the tonic discharge pattern of GP, STN and SNr neurons. Our results are the first to demonstrate that dopamine through activation of D2Rs located in the GP plays an important role in the modulation of GP-STN and GP-SNr neurotransmission and consequently controls STN and SNr neuronal firing. Moreover, we provide evidence that dopamine modulate the firing rate but not the pattern of GP neurons, which in turn control the firing rate, but not the pattern of STN and SNr neurons.

Intraoperative dopamine release during globus pallidus internus stimulation in Parkinson's disease

It is still unclear whether dopamine (DA) levels correlate with Parkinson's disease (PD) severity or play a role in the mechanisms of high-frequency stimulation (HFS). We have used microdialysis to record pallidal DA in 5 patients with PD undergoing microelectrode-guided pallidotomy. We found that patients with more severe disease and, consequently, lower pallidal DA did poorly after pallidal lesions. In the operating room, 4 of 5 patients had a significant increase in DA levels during HFS (600%, on average). To test the hypothesis that DA was important for the effects of stimulation, we correlated the amelioration in rigidity observed in the operating room with pallidal DA release. Though rigidity was 56% better during stimulation, no correlation was found between such an improvement and DA release. These findings suggest that additional mechanisms not directly dependent on pallidal DA release may be involved in the clinical effects of HFS of the globus pallidus internus.

ErbB inhibitors ameliorate behavioral impairments of an animal model for schizophrenia: implication of their dopamine-modulatory actions

Ligands for ErbB receptors, including epidermal growth factor (EGF) and neuregulin-1, have a neurotrophic activity on midbrain dopaminergic neurons and are implicated in the pathophysiology of schizophrenia. Although ErbB kinase inhibitors ameliorate behavioral deficits of the schizophrenia model that was established by hippocampal lesioning of rat pups, the antipsychotic action of ErbB kinase inhibitors and its general applicability to other models are not fully characterized. Using a different animal model, here, we examined whether and how ErbB kinase inhibitors ameliorate the behavioral endophenotypes relevant to schizophrenia. The animal model for schizophrenia was prepared by exposing neonatal rats to the cytokine EGF. Intraventricular infusion of the ErbB1 inhibitors ZD1839 and PD153035 in these animals ameliorated the deficits in startle response and prepulse inhibition in a dose-dependent manner. The deficits of latent inhibition of fear learning were also alleviated by ZD1839 with its limited effects on body weight gain or locomotor activity. ZD1839 infusion also decreased the busting activity of nigral dopamine (DA) neurons and reduced pallidal DA metabolism, a result that mimics the anti-dopaminergic profile of risperidone and haloperidol in this brain region. ErbB inhibitors appear to have anti-dopaminergic actions to alleviate some of the behavioral deficits common to animal models for schizophrenia.

Accumbal and pallidal dopamine, glutamate and GABA overflow during cocaine self‐administration and its extinction in rats

We investigated the changes in dopamine (DA), glutamate and γ-aminobutyric acid (GABA) during cocaine self-administration in rats implanted with guide cannulae into the nucleus accumbens and ventral pallidum. After stabilized cocaine self-administration, separate groups of rats underwent extinction (10 days) procedure in which cocaine infusion was replaced by saline injections. With using a 'yoked' procedure, the effects of cocaine or its withdrawal on the level of neurotransmitters were evaluated by dual-probe microdialysis. Repeated cocaine administration reduced basal glutamate levels in the nucleus accumbens and ventral pallidum, whereas it did not affect basal accumbal DA levels. Only rats that self-administered cocaine had increased basal GABA overflow in both examined brain structures. Active or passive cocaine administration elevated extracellular accumbal DA, however, the extent of cocaine-evoked DA level was significantly higher in rats that self-administered cocaine while both groups of animals showed also an attenuation of GABA level in the nucleus accumbens. On day 10 of extinction training, rats previously given cocaine revealed decreases in the basal accumbal concentration of glutamate while the basal GABA levels were significantly enhanced as compared with baseline of saline-yoked controls. Potassium depolarization delayed the reduction of the accumbal and pallidal extracellular glutamate levels in the active and passive cocaine groups. The present data indicate that changes in DA and GABA neurotransmission during maintenance phase mirror the motivational aspects of cocaine intake. Depending on acute (24 hours) or late (10 days) cocaine withdrawal, different neurotransmitter systems (i.e. glutamate or GABA) seem to be involved.

Pallidal Hyperdopaminergic Innervation Underlying D2 Receptor-Dependent Behavioral Deficits in the Schizophrenia Animal Model Established by EGF

Epidermal growth factor (EGF) is one of the ErbB receptor ligands implicated in schizophrenia neuropathology as well as in dopaminergic development. Based on the immune inflammatory hypothesis for schizophrenia, neonatal rats are exposed to this cytokine and later develop neurobehavioral abnormality such as prepulse inhibition (PPI) deficit. Here we found that the EGF-treated rats exhibited persistent increases in tyrosine hydroxylase levels and dopamine content in the globus pallidus. Furthermore, pallidal dopamine release was elevated in EGF-treated rats, but normalized by subchronic treatment with risperidone concomitant with amelioration of their PPI deficits. To evaluate pathophysiologic roles of the dopamine abnormality, we administered reserpine bilaterally to the globus pallidus to reduce the local dopamine pool. Reserpine infusion ameliorated PPI deficits of EGF-treated rats without apparent aversive effects on locomotor activity in these rats. We also administered dopamine D1-like and D2-like receptor antagonists (SCH23390 and raclopride) and a D2-like receptor agonist (quinpirole) to the globus pallidus and measured PPI and bar-hang latencies. Raclopride (0.5 and 2.0 µg/site) significantly elevated PPI levels of EGF-treated rats, but SCH23390 (0.5 and 2.0 µg/site) had no effect. The higher dose of raclopride induced catalepsy-like changes in control animals but not in EGF-treated rats. Conversely, local quinpirole administration to EGF-untreated control rats induced PPI deficits and anti-cataleptic behaviors, confirming the pathophysiologic role of the pallidal hyperdopaminergic state. These findings suggest that the pallidal dopaminergic innervation is vulnerable to circulating EGF at perinatal and/or neonatal stages and has strong impact on the D2-like receptor-dependent behavioral deficits relevant to schizophrenia.

Modulation of the activity of globus pallidus by dopamine D1-like receptors in parkinsonian rats

Morphological studies have shown that the globus pallidus receives dopaminergic innervation from the collaterals of nigrostriatal fibers. Dopamine D1-like receptors are expressed at both pre- and postsynaptic membrane. In the present study, we investigate the in vivo electrophysiological and behavioral effects of pallidal dopamine D1-like receptors in parkinsonian rats. On the lesioned side of 6-hydroxydopamine (6-OHDA) parkinsonian rats, micropressure ejection of dopamine D1-like receptor agonist, SKF38393, increased (88.2 ± 18.6%) the firing rate in 10 out of the 32 pallidal neurons, but decreased (49.5 ± 6.1%) the firing rate in 14 out of the 32 neurons. Furthermore, on the unlesioned side of parkinsonian rats, SKF38393 increased (43.0 ± 6.3%) the firing rate in 9 out of the 30 pallidal neurons, but decreased (47.1 ± 4.8%) the firing rate in 13 out of the 30 neurons. In behaving rats, unilateral microinjection of SKF38393 led to contralateral deflection in the presence of systemic haloperidol administration. The selective dopamine D1-like receptor antagonist, SCH23390, blocked both SKF38393-induced electrophysiological and behavioral effects. Combining electrophysiological and behavioral findings, we concluded that activation of dopamine D1-like receptors modulates the activity of globus pallidus neurons in rats.

Microdialysis and mass spectrometric monitoring of dopamine and enkephalins in the globus pallidus reveal reciprocal interactions that regulate movement.

Pallidal dopamine, GABA and the endogenous opioid peptides enkephalins have independently been shown to be important controllers of sensorimotor processes. Using in vivo microdialysis coupled to liquid chromatography-mass spectrometry and a behavioral assay, we explored the interaction between these three neurotransmitters in the rat globus pallidus. Amphetamine (3 mg/kg i.p.) evoked an increase in dopamine, GABA and methionine/leucine enkephalin. Local perfusion of the dopamine D(1) receptor antagonist SCH 23390 (100 μM) fully prevented amphetamine stimulated enkephalin and GABA release in the globus pallidus and greatly suppressed hyperlocomotion. In contrast, the dopamine D(2) receptor antagonist raclopride (100 μM) had only minimal effects suggesting a greater role for pallidal D(1) over D(2) receptors in the regulation of movement. Under basal conditions, opioid receptor blockade by naloxone perfusion (10 μM) in the globus pallidus stimulated GABA and inhibited dopamine release. Amphetamine-stimulated dopamine release and locomotor activation were attenuated by naloxone perfusion with no effect on GABA. These findings demonstrate a functional relationship between pallidal dopamine, GABA and enkephalin systems in the control of locomotor behavior under basal and stimulated conditions. Moreover, these findings demonstrate the usefulness of liquid chromatography-mass spectrometry as an analytical tool when coupled to in vivo microdialysis.

Cardiac Arrest Following Foreign-Body Aspiration

<b>Background: </b> Patients with Parkinson disease (PD) may be akinetic/rigid, be tremor dominant, or have comparable severity of these motor symptoms (classic). The pathophysiologic basis of different PD phenotypes is unknown. This study assessed pallidal and striatal dopamine level patterns in different motor subgroups of PD and normal control brains. <b>Methods: </b> Globus pallidus and striatum dopamine (DA) levels were measured with high performance liquid chromatography in eight autopsy confirmed PD and five control frozen brains. <b>Results: </b> DA levels in the external globus pallidus (GPe) of normal brains were nearly six times greater than in the internal pallidum (GPi). In PD, the mean loss of DA was marked (−82%) in GPe and moderate (−51%) in GPi. DA loss of variable degree was seen in different subdivisions of GPe and GPi in PD; however, DA levels were near normal in the ventral (rostral and caudal) GPi of PD cases with prominent tremor. There was marked loss of DA (−89%) in the caudate and severe loss (−98.4%) in the putamen in PD. The pattern of pallidal DA loss did not match the putaminal DA loss. <b>Conclusion: </b> There is sufficient loss of dopamine (DA) in external globus pallidus and the internal globus pallidum (GPi) as may contribute to the motor manifestations of Parkinson disease (PD). The possible functional disequilibrium between GABAergic and DAergic influences in favor of DA in the caudoventral parts of the GPi may contribute to resting tremor in tremor dominant and classic PD cases. <b>GLOSSARY: </b><b>CN</b> = caudate nucleus; <b>DA</b> = dopamine; <b>GPe</b> = external globus pallidus; <b>GPi</b> = internal globus pallidum; <b>LB</b> = Lewy body; <b>MDCS</b> = Movement Disorder Clinic in Saskatoon; <b>PD</b> = Parkinson disease; <b>PUT</b> = putamen; <b>VTA</b> = ventral tegmental area.

Different effects of dopamine D1 receptor on the firing of globus pallidus neurons in rats

The globus pallidus in rodents, equivalent to the external globus pallidus in primates, plays an important role in movement regulation. Morphological studies have indicated that the globus pallidus receives dopamine innervation from the collaterals of nigrostriatal fibers. To investigate the direct electrophysiological effects of dopamine D1 receptors in the globus pallidus, in vivo extracellular recordings were performed in the present study. In 25 out of 58 globus pallidus neurons, micro-pressure ejection of 5mM SKF38393 increased the spontaneous firing rate from 9.8±1.9Hz to 14.3±2.5Hz. The average increase was 61.5±8.3% (P<0.001). In another 12 out of the 58 globus pallidus neurons, micro-pressure ejection of SKF38393 decreased the spontaneous firing rate from 4.7±1.2Hz to 2.1±0.6Hz. The average decrease was 52.1±6.7% (P<0.05). Micro-pressure ejection of SKF38393 did not alter the firing rate significantly in the left 21 globus pallidus neurons. The present findings may provide a rational for further investigations into the potential of pallidal dopamine D1 receptor in the treatment of Parkinson's disease.

Effects of self-administered cocaine in rats on accumbal and pallidal dopamine, glutamate and GABA levels

Effects of self-administered cocaine in rats on accumbal and pallidal dopamine, glutamate and GABA levels

Globus pallidus dopamine and Parkinson motor subtypes

Patients with Parkinson disease (PD) may be akinetic/rigid, be tremor dominant, or have comparable severity of these motor symptoms (classic). The pathophysiologic basis of different PD phenotypes is unknown. This study assessed pallidal and striatal dopamine level patterns in different motor subgroups of PD and normal control brains. Globus pallidus and striatum dopamine (DA) levels were measured with high performance liquid chromatography in eight autopsy confirmed PD and five control frozen brains. DA levels in the external globus pallidus (GPe) of normal brains were nearly six times greater than in the internal pallidum (GPi). In PD, the mean loss of DA was marked (-82%) in GPe and moderate (-51%) in GPi. DA loss of variable degree was seen in different subdivisions of GPe and GPi in PD; however, DA levels were near normal in the ventral (rostral and caudal) GPi of PD cases with prominent tremor. There was marked loss of DA (-89%) in the caudate and severe loss (-98.4%) in the putamen in PD. The pattern of pallidal DA loss did not match the putaminal DA loss. There is sufficient loss of dopamine (DA) in external globus pallidus and the internal globus pallidum (GPi) as may contribute to the motor manifestations of Parkinson disease (PD). The possible functional disequilibrium between GABAergic and DAergic influences in favor of DA in the caudoventral parts of the GPi may contribute to resting tremor in tremor dominant and classic PD cases.

Effects of physiological and pharmacological stimuli on dopamine release in the rat globus pallidus

A major aspect of understanding functions of the globus pallidus (GP) within the basal ganglia is the significance of its dopamine innervation. Here, we used in vivo-microdialysis in rats to characterize pallidal dopamine release in response to a number of physiological and pharmacological stimuli known to activate dopamine neurons. Results reveal that an aversive stimulus, i.e. handling for 20 min, significantly increased dialysate dopamine in the globus pallidus to about 130% of baseline levels. Likewise, a novel and appetitive stimulus, i.e. presentation of unfamiliar, palatable food, significantly elevated pallidal dopamine to about 150% of baseline levels both in rats which did and did not consume the food reward. These findings provide evidence that increases of dopamine (DA) efflux may largely reflect stimulus saliency implicating an involvement of pallidal dopamine signalling in control of behaviour governed by salient stimuli. Results further showed that reverse microdialysis of d-amphetamine and cocaine in augmenting concentrations of 0.1–100 μM elevated dialysate dopamine in a concentration-dependent manner suggesting a role of pallidal dopamine in mediating behavioural effects of psychostimulant drugs.

Modulation of ventral pallidal dopamine and glutamate release by the intravenous anesthetic propofol studied by in vivo microdialysis

The intravenous anesthetic propofol is reported to have various psychological side effects as hallucinations, sexual disinhibition, or euphoria. Hedonic and rewarding states like these are modulated by the dopaminergic system in the nucleus accumbens, prefrontal cortex and also in the ventral pallidum and by the glutamatergic system in the neocortex and limbic system. In the present study, propofol was administered either alone or in combination with the GABAA receptor antagonist bicuculline via reverse microdialysis into the ventral pallidum of freely moving rats. Dialysis fractions were taken every 20 min and analyzed for dopamine and glutamate using high performance liquid chromatography. Application of propofol decreased dopamine levels in the ventral pallidum. This effect seems to be mainly mediated through GABAA receptors, since it was compensated by the GABAA receptor antagonist bicuculline. Propofol and propofol plus bicuculline exerted no effect on glutamate release in this brain region. The reduced dopamine release in ventral pallidum was most probably mediated through a GABAergic feedback loop from the ventral pallidum via the nucleus accumbens to the dopaminergic neurons of the ventral tegmental area or by long loop feedback. As an increase but not a decrease of dopamine release in the ventral pallidum is involved in hedonic and rewarding properties, similar symptoms induced by propofol seem to be unrelated to an action of propofol in the ventral pallidum.

Changes in extracellular dopamine in the rat globus pallidus induced by typical and atypical antipsychotic drugs

Typical antipsychotic drugs with a high extrapyramidal motor side-effects liability markedly increase extracellular dopamine in the caudate-putamen, while atypical antipsychotic drugs with a low incidence of extrapyramidal motor side-effects have less pronounced stimulating actions on striatal dopamine. Therefore, it has been suggested that the extrapyramidal motor side-effects liability of antipsychotic drugs (APD) is correlated with their ability to increase extracellular dopamine in the caudate-putamen. The globus pallidus (GP) is another basal ganglia structure probably mediating extrapyramidal motor side-effects of typical antipsychotic drugs. Therefore, the present study sought to determine whether extracellular dopamine in the globus pallidus might be a further indicator to differentiate neurochemical actions of typical and atypical antipsychotic drugs. Using in vivo microdialysis we compared effects on pallidal dopamine induced by typical and atypical antipsychotic drugs in rats. Experiment I demonstrated that systemic administration of haloperidol (1 mg/kg; i.p.) and clozapine (20 mg/kg; i.p.) induced a significant pallidal dopamine release to about 160 and 180% of baseline, respectively. Experiment II revealed that reverse microdialysis of raclopride and clozapine using a cumulative dosing regimen did not stimulate extracellular dopamine in the globus pallidus if low (1 μM) or intermediate (10 and 100 μM) concentrations were used. Only at a high concentration (1000 μM), raclopride and clozapine induced a significant pallidal dopamine release to about 130 and 300% of baseline values, respectively. Thus, effects of typical and atypical antipsychotic drugs on pallidal dopamine were similar and thus, may not be related to their differential extrapyramidal motor side-effects liability. Furthermore, the finding that reverse microdialysis of raclopride over a wide range of concentrations did not stimulate pallidal dopamine concentrations tentatively suggests that pallidal dopamine release under basal conditions is not regulated by D2 autoreceptors.

Dopaminergic innervation of the rat globus pallidus characterized by microdialysis and immunohistochemistry.

The present study examined the dopaminergic innervation of the rat globus pallidus by in vivo microdialysis and immunohistochemistry in more detail. Using tyrosine hydroxylase immunohistochemistry, two classes of dopaminergic fibers were distinguished morphologically in the globus pallidus. Unilateral infusion of 6-hydroxydopamine into the substantia nigra produced a loss of dopaminergic fiber density in the globus pallidus which was correlated with the nigral extent of the lesion. These findings are in line with the notion that a degenerative loss of nigral dopaminergic cell bodies might also affect the dopamine input of extrastriatal structures such as the globus pallidus. Using in vivo microdialysis, we tested whether dopamine measured in the globus pallidus is of neuronal origin. Perfusion of tetrodotoxin induced a strong and transient decrease of pallidal dopamine. The tetrodotoxin-sensitivity of pallidal dopamine demonstrates the functional significance of the nigropallidal dopaminergic innervation.

D2 antagonist-induced c- fos in an identified subpopulation of globus pallidus neurons by a direct intrapallidal action

Much research now supports the view that the dopaminergic innervation of the globus pallidus external segment (GP) influences basal ganglia information processing via pallidal dopamine (DA) D2, D3, and possibly D1 receptors. Systemic DA agonists, or systemic or intrapallidal dopamine D2-class antagonist administration, can induce immediate early gene expression (IEG) in the rat GP. In view of the distinct chemical phenotypes and axonal projections of the GP neurons, it is important to characterize the population(s) of pallidal neurons responding to local DA manipulations. Parvalbumin (PV) immunostaining was used to identify one of the two principal GP neuron populations. Awake, behaving rats received intrapallidal infusions of the dopamine D2 antagonist sulpiride (50 or 100 ng), the D1-class antagonist SCH-23390 (100 ng), the D2-class agonist quinpirole (500 ng), the GABA A antagonist picrotoxin (0.25, 0.5 or 1 μg) or bicuculline (20 ng), the GABA A agonist muscimol (15 ng) or vehicle. Intrapallidal GABA manipulations were used to assess the likelihood that the effects of the DAergic drugs on Fos induction occurred secondarily to altering intrapallidal GABA release. Using Fos and PV double immunolabeling procedures, we found that several treatments induced GP Fos, but that intrapallidal sulpiride induced Fos almost exclusively in PV-lacking pallidal neurons. No other intrapallidal drug-induced Fos showed similar population specificity. These results support evidence suggesting that GP DA can play a unique and critical role in modulating pallidal neuron function, and that the cessation of pallidal dopamine transmission can activate gene expression within the pallidal neuron subpopulation that maintains extensive axonal projections to caudate-putamen.

Dopamine D 1 or D 2 receptor blockade in the globus pallidus produces akinesia in the rat

In the present study, the involvement of dopamine D 1 and D 2 receptors in the dorsal globus pallidus (GP) in motor control was investigated in rats. Results show that bilateral microinfusions of the dopamine D 1 receptor antagonist SCH23390 or the dopamine D 2 antagonist S(−)-sulpiride into the GP induced akinesia determined by means of the catalepsy test. These findings indicate that pallidal dopamine D 1 and D 2 receptors are critically involved in the control of motor behaviour. The findings further imply that defective dopaminergic transmission in the GP might contribute to akinesia due to lesion- or drug-induced dopamine hypofunction in experimental animals and in neurodegenerative diseases, e.g. Parkinson’s disease, affecting the nigrostriatal dopamine system.

Blockade of dopamine D 2, but not of D 1 receptors in the rat globus pallidus induced Fos-like immunoreactivity in the caudate-putamen, substantia nigra and entopeduncular nucleus

In the present study, we investigated Fos-like immunoreactivity (FLI) evoked by pallidal dopamine (DA) D 1 and D 2 receptor blockade in the caudate-putamen (CPu), substantia nigra (SN) and entopeduncular nucleus (EP), i.e. major target areas of pallidal efferents. Results demonstrate that infusion of the selective D 1 antagonist SCH23390 (1 and 4 μg/0.5 μl) into the globus pallidus (GP) did not induce FLI in the CPu, SN and EP. In contrast, intrapallidal infusion of a low dose of the selective D 2 antagonist S(−)-sulpiride (15 μg/0.5 μl) induced FLI restricted to the CPu. A higher dose of intrapallidal S(−)-sulpiride (25 μg/0.5 μl) induced FLI in the CPu as well as in the SN and EP. These findings add further evidence to notion that the GP plays a central role in the basal ganglia circuitry and demonstrate an involvement of extrastriatal DA via D 2 receptors.

Dopamine D 1/D 2 agonists injected into nucleus accumbens and ventral pallidum differentially affect locomotor activity depending on site

Ventral pallidal dopamine has been recently shown to play an important role in psychostimulant reward and locomotor activation. The aim of the present study was to compare the roles of ventral pallidal D 1 and D 2 receptors in evoking locomotor activity with those in the nucleus accumbens. The D 1 agonist SKF 38393 and the D 2 agonist quinpirole hydrochloride (0.3–3 μg/0.5 μl) were bilaterally injected into ventral pallidum or nucleus accumbens through pre-implanted cannulae. In the ventral pallidum, 0.3–1 μg SKF 38393 increased locomotor activity while 3 μg had no effect; 3 μg quinpirole suppressed locomotion while 0.3–1 μg had no effect. Locomotor activity induced by an equigram (0.3 μg) mixture of SKF 38393 and quinpirole, while significantly higher than that induced by 0.3 μg quinpirole was not significantly higher than that induced by 0.3 μg SKF 38393 alone. At the 3 μg dose, SKF 38393 injections into anterior ventral pallidum increased activity; injections into posterior ventral pallidum decreased activity. In the nucleus accumbens, 0.3–3 μg SKF 38393 dramatically increased locomotor activity while quinpirole moderately increased locomotion. In the group that had previously received the full quinpirole dose range, injection of the equigram (0.3 μg) mixture of SKF 38393 and quinpirole induced locomotor activation which was higher than that induced by either drug alone or by the addition of the effect of each drug alone, i.e. synergy occurred. Moreover, rats that had previously received SKF 38393 developed a sensitized locomotor response to subsequent SKF 38393, quinpirole or the mixture of these two drugs. The difference in locomotor response to dopamine agonists between the ventral pallidum and nucleus accumbens is consistent with electrophysiological evidence collected at these two sites. These findings suggest that, unlike the nucleus accumbens, where D 1 and D 2 receptor activation may facilitate each other to induce a synergistic effect on locomotor activity, ventral pallidal D 1 and D 2 receptors may be located on different neurons and coupled with different, if not opposite, behavioral output.

GABAergic modulation of ventral pallidal dopamine release studied by in vivo microdialysis in the freely moving rat

GABAergic modulation of ventral pallidal dopamine release studied by in vivo microdialysis in the freely moving rat