Right-left asymmetry of D1- and D2-receptor density is lost in the basal ganglia of old rats

In the present study a left-right asymmetry in both D₁ and D₂-receptor density in the caudate-putamen nucleus is shown and a lateralisation of D₂-receptor distribution in the accunbens nucleus is also described. In old animals in which D₁- and D₂-receptors density is decreased, the dopamine receptor asymmetries are lost.     

Axonal transport of angiotensin-converting enzyme in the rat striatonigral pathway

We analyzed the transport of angiotensin-converting enzyme (kininase II, EC 3.4.15.1) in the striatonigral pathway by quantitative autoradiography using the specific converting enzyme inhibitor, ¹²⁵I-351A. ¹²⁵I-351A binding was studied at different time intervals after knife cut lesions of the striatonigral pathway. Twenty-four h after the lesion, accumulations of ¹²⁵I-351A binding sites were observed both rostral and caudal to the lesioned site. No change in ¹²⁵I-351A binding was observed at this time in the caudate putamen and substantia nigra. Ten days after the lesion, a significant decrease (58%) in ¹²⁵I-351A binding was found in the pars reticulata of the ipsilateral substantia nigra. These results suggest that the angiotensin-converting enzyme is transported axonally in the rat striatonigral pathway.     

Use of positron emission tomography to measure the effects of nalmefene on D1 and D2 dopamine receptors in rat brain

Positron emission tomography (PET) has been used in humans and in non-human primates to image and measure radioligand binding to neuroreceptors. The present study evaluated the feasibility of performing high-resolution PET experiments in a rodent model to measure receptor kinetics. The effects of acute and chronic administration of the opioid antagonist, nalmefene, on the binding activity of [¹¹C]SCH23390 and [¹¹C]N-methylspiperone at D₁ and D₂ dopamine receptors, respectively, was investigated in the rat. The interaction between central opioid and dopaminergic systems has been the focus of much attention due to their interactive role in mediating reinforcement and locomotor activity. In the present study, adult male Sprague–Dawley rats received either a single injection of 10 mg/kg of nalmefene or control vehicle solution 1 h prior to the PET scan or were chronically administered 10 mg/kg/day of nalmefene or vehicle for 7 days by an osmotic minipump. Following acute administration of nalmefene, the binding potential of [¹¹C]SCH23390 in the striatum was significantly increased. No changes in [¹¹C]N-methylspiperone binding were found. Following chronic nalmefene administration, no significant change in either [¹¹C]SCH23390 binding potential or [¹¹C]N-methylspiperone binding was detected. These results suggest that nalmefene administration produces transient changes in the binding potential of D₁-receptors in the striatum that are normalized after 1 week of steady-state administration.     

Autoradiographic localization of D1 dopamine receptors in the rat brain with [H]SCH 23390

The regional distribution of D₁ dopamine (DA) receptors in the rat brain has been studied by quantitative autoradiography using the specific D₁ antagonist [³H]SCH 23390 as a ligand. The binding of [³H]SCH 23390 to striatal sections was saturable, stereospecific, reversible and of high affinity (K_d = 2.05nM); it occurred at single population of sites and possessed the pharmacological features of the D₁ DA receptor. The highest densities of [³H]SCH 23390 binding sites were found in the caudate-putamen, olfactory tubercle, nucleus accumbens and substantia nigra (especially in the pars compacta). High densities were also observed in the nucleus interstitialis striae terminalis, the anterior olfactory nucleus, the entopeduncular nucleus, the subthalamic nucleus, the claustrum and the amygdalohippocampal area. An intermediate labelling was found in the anteromedial and suprarhinal DA terminal fields of the cerebral cortex, the basolateral, medial and lateral amygdaloid nuclei, the endopiriform nucleus, the primary olfactory cortex, the globus pallidus, the superior colliculus (especially the superficial layer), the nucleus amygdaloideus corticalis and the dorsal hippocampus (molecular layer of the CA₁ and dentate gyrus). In the anteromedial and suprarhinal cortices, [³H]SCH 23390 binding was more concentrated in layers V and VI. Moderate levels of [³H]SCH 23390 were found in the thalamus, hypothalamus, the habenula, the ventral tegmental area, the posterior cingulate and entorhinal cortices, the supragenual dopamine terminal system and the cerebellum (molecular layer). This regional distribution of [³H]SCH 23390 closely correlated (except for the cerebellum) with the reported distribution of dopaminergic terminals. The topographical distribution of [³H]SCH 23390 has also been studied in detail in striatal subregions. The density of D₁ receptors was much greater in the ventrolateral sector and medial margin of the striatum than in the ventromedial and dorsolateral sectors. A rostrocaudal decrease in the densities of D₁ sites was also found along the rostrocaudal axis of the caudate-putamen. These lateral to medial and anteroposterior gradients overlapped with the density of the dopaminergic afferents.     

The involvement of dopamine in nociception: the role of D1 and D2 receptors in the dorsolateral striatum

Determination of the neuroanatomical and neurochemical factors that contribute to nociception is an essential element in the study and treatment of pain. Several lines of evidence have implicated nuclei and neurotransmitters within the basal ganglia in nociception. For example, previous studies have shown that dopamine receptors in the striatum are involved in acute nociception, however, it remains to be determined if dopamine receptors in the dorsolateral striatum are involved in persistent nociception. The purpose of the present study was therefore to determine whether activation or antagonism of dopamine receptors in the dorsolateral striatum influences the nociceptive responses of rats in the formalin test, a model of persistent pain. It was found that micro-injection of the non-selective dopamine antagonist haloperidol into the dorsolateral striatum increases formalin-induced nociception whereas injection of the non-selective dopamine agonist apomorphine reduces formalin-induced nociception. Injection of the D₁ antagonist SCH23390 or the D₁ agonist SKF38393 does not affect formalin-induced nociception. In contrast, injection of the D₂ antagonist eticlopride enhances formalin-induced nociception, whereas injection of the D₂ agonist quinpirole reduces formalin-induced nociception. These results provide additional evidence that dopamine receptors in the striatum are involved in nociception. Furthermore, this study strongly suggests that D₂, but not D₁, dopamine receptors in the dorsolateral striatum are involved in modulation of persistent nociception.     

Roles of dopamine D1 receptors inΔ-tetrahydrocannabinol-induced expression of Fos protein in the rat brain

We examined whether administration ofΔ⁹-tetrahydrocannabinol (THC) induces the expression of Fos protein or not in the rat brain. A single administration of 3.2 and 10 mg/kg THC produced a dose-dependent and significant increase in Fos-immunoreactive cells in the striatum, particularly in its dorsomedial portions. The peak increase was reached 2 h after THC treatment and was absent at 8 h. Fos induction was also observed in the nucleus accumbens after administration of 10 mg/kg THC. However, in the globus pallidus, hippocampus and substantia nigra pars reticula, abundant in cannabinoid receptors, there were few or no Fos-immunoreactive cells induced by 10 mg/kg THC. SCH-23390, a selective dopamine D₁ receptor antagonist, at 0.32 mg/kg produced a significant block of the effects of THC on Fos expression in the striatum and the nucleus accumbens. Administration of 100 mg/kg (-)-sulpiride, a selective dopamine D₂ receptor antagonist, failed to block the effect of THC on Fos expression in both the striatum and the nucleus accumbens. These findings indicate that THC induces the expression of Fos protein and that this expression is mediated at least by dopamine D₁ receptors.     

Dopamine D1 receptors are involved in the modulation of D2 receptors induced by cholecystokinin receptor subtypes in rat neostriatal membranes

The action of cholecystokinin octapeptide (CCK-8) on rat neostriatal dopamine (DA) D₂ receptors was evaluated in membrane binding experiments. 0.1 nM of CCK-8 inreased theK_d value of the D₂ agonist [³H]N-propylnorapomorphine (NPA) binding sites by 42%. The CCK_B antagonist PD134308 blocked this action. Kinetic analysis demostrated that this effect of CCK-8 was related to a reduction by 45% of the association rate constant of [³H]NPA. In contrast, 1 nM of CCK-8 decreased theK_H and theK_L values of DA for the D₂ antagonist [³H]raclopride binding sites by 56% and 50%, respectively. Both the CCK_A antagonist L364718 and the CCK_B antagonist PD134308 blocked this effect. The D₁ antagonist SCH23390 counteracted the CCK-8 induced decrease in theK_H and theK_L values of DA, and allowed 1 nM of CCK-8 to produce a significant increase in the IC₅₀ value of NPA for the [³H]raclopride binding sites. These results indicate that CCK-8 can reduce the affinity of the neostriatal D₂ agonist binding sites, but increase the affinity of D₂ receptors for DA. D₁ receptors may exert a switching role in the modulation of the neostriatal D₂ receptors by the CCK receptors.     

Presynaptic and postsynaptic D1 dopamine receptors in the nigrostriatal system of the rat brain: a quantitative autoradiographic study using the selective D1 antagonist [H]SCH 23390

Ibotenic acid lesions of the caudate-putamen in rat brain resulted in dramatic reductions in [³H]SCH 23390 binding in both the ipsilateral caudate-putamen and substantia nigra reticulata as assessed by quantitative autoradiography. Nigral ibotenic acid and 6-hydroxydopamine lesions did not significantly alter the binding in either structure. This indicates that D₁ receptors in the caudate-putamen are postsynaptic on striatal neurons, while those in the substantia nigra reticulata are presynaptic on nerve terminals originating in the caudate-putamen.     

Involvement of dopamine D1 and D2 receptors in the ethanol-associated place preference in rats exposed to conditioned fear stress

The present study was designed to investigate: (1) the involvement of dopamine D₁ and D₂ receptors, and (2) the roles of these receptors and endogenous opioid systems (endorphinergic and enkephalinergic systems) in the ethanol-induced place preference in rats exposed to conditioned fear stress using the conditioned place preference paradigm. The administration of ethanol (300 mg/kg, i.p.) induced a significant place preference. The selective D₁ receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H3-benzazepine)hydrochloride (SCH23390; 0.01 and 0.03 mg/kg, s.c.) and the selective D₂ receptor antagonist S(−)-5-(aminosulfonyl)-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride; 20 and 40 mg/kg, s.c.) significantly attenuated the ethanol-induced place preference. The administration of ethanol (75 mg/kg, i.p.) tended to produce a place preference, but this effect was not significant. SCH23390 (0.03 mg/kg, s.c.) and sulpiride (40 mg/kg, s.c.) significantly attenuated the enhancement of the ethanol (75 mg/kg, i.p.)-induced place preference produced by the μ-opioid receptor agonist morphine (0.1 mg/kg, s.c.). In addition, SCH23390 (0.03 mg/kg, s.c.) also significantly attenuated the enhancement of the ethanol (75 mg/kg, i.p.)-induced place preference produced by the selective δ-opioid receptor agonist 2-methyl-4aα-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aα-octahydroquinolino[2,3,3,-g]isoquinoline (TAN-67; 20 mg/kg, s.c.). On the other hand, sulpiride (40 mg/kg) had no significant effect on the enhancement of the ethanol (75 mg/kg, i.p.)-induced place preference produced by TAN-67. These results suggest that D₁ and D₂ receptors may be involved in the rewarding mechanism of ethanol under psychological stress. In addition, D₁ receptors may participate in the rewarding effect of ethanol modulated by the activation of μ- and δ-opioid receptors, whereas D₂ receptors may participate in the rewarding effect of ethanol modulated by the activation of μ-opioid receptors, but not in that modulated by the activation of δ-opioid receptors.     

Topographic nonoverlapping distribution of D1 and D2 dopamine receptors in the amygdaloid nuclear complex of the rat brain.

The distribution of D1 and D2 dopamine (DA) receptors in the nuclei and subnuclear zones of the rat amygdaloid complex was mapped using quantitative light microscopic autoradiography. [125I]iodosulpiride and [125I]SCH 23982 (in the presence of 50 nM ketanserin) were used to label D2 and D1 DA receptors, respectively. The DA receptor subtypes exhibited a topographic, nonoverlapping distribution which generally conformed to the cytoarchitectonic boundaries of the component nuclei and subnuclear zones of the amygdaloid complex. The highest density of [125I]iodosulpiride binding sites was observed in the main intercalated cell group and the central amygdaloid nucleus where a medial to lateral gradient of binding sites was localized to its subnuclear zones. [125I]SCH 23982 binding sites were localized in the main intercalated cell group and the basolateral amygdaloid nucleus with a uniform low density in the central nucleus. The functional topography of mesoamygdaloid DA neurons may therefore be mediated, in part, at the level of DA receptor subtypes. The pattern of distribution of [125I]iodosulpiride binding sites in subdivisions of the central amygdaloid nucleus and bed nucleus of the stria terminalis suggests that the functions of the "extended amygdala," a major system of the functional organization of the basal forebrain, may be regulated by DA afferents at multiple key sites of D2 receptor action.     

Sensitization of amphetamine-induced stereotyped behaviors during the acute response: role of D1 and D2 dopamine receptors

During the response to an injection of amphetamine, rapid changes occur in the ability of the drug to induce stereotyped behaviors. This enhanced responsivity does not involve changes in the caudate–putamen or nucleus accumbens extracellular dopamine response, but appears to require activation of dopamine receptors. In the present studies we examined the role that D₁ and D₂ dopamine receptors might play in the development and expression of the enhanced stereotypy response. In one series of experiments we used the dopamine agonists, SKF 82958 and quinpirole as relatively selective probes at D₁ and D₂ dopamine receptors, respectively, to test for changes in dopamine receptor sensitivity following a pretreatment (‘priming') with 4.0 mg/kg amphetamine. Doses of both SKF 82958 and quinpirole which were sub-threshold to induce perseverative behaviors in control animals, promoted stereotyped behaviors in amphetamine-primed animals, suggesting an enhanced sensitivity of both D₁ and D₂ receptors. In a second series of experiments, we sought to determine whether priming with these relatively selective dopamine receptor agonists, as well as the mixed D₁/D₂ agonist, apomorphine, would result in an enhanced stereotypy response to the subsequent administration of non-stereotypy producing doses of amphetamine (0.5–1.5 mg/kg). Priming with the dopamine receptor agonists each resulted in an enhanced amphetamine-induced stereotypy response. These results indicate that both D₁ and D₂ dopamine receptors contribute to both the development and the expression of the altered stereotypy responsivity, though several dose- and time-related observations suggest that other mechanisms likely contribute as well. Because these changes are apparent during the amphetamine response, they may have important implications for the evolving behavioral alterations which result when stimulants are administered in a binge pattern of drug abuse.     

Direct demonstration of D1 dopamine receptors in the bovine parathyroid gland using the D1 selective antagonist [125I]-SCH 23982

The presence of D1 dopamine receptors in the parathyroid gland has been proposed based on the demonstration of dopaminergic regulation of adenylate cyclase activity and parathyroid hormone release in dispersed bovine parathyroid cells. Using a radioiodinated D1 selective antagonist [125I]-SCH 23982, we have now directly labeled and characterized the D1 dopamine receptors in bovine parathyroid gland membranes. [125I]-SCH 23982 binds in a saturable manner with high affinity and low nonspecific binding to membranes prepared from bovine parathyroid glands. D1 dopamine receptors are present in this preparation at a concentration of approximately 130 fMoles/mg protein and [125I]-SCH 23982 binding increases with increasing protein concentration in a linear fashion. Determination of the Kd using the association (k1) and dissociation (k-1) rate constants revealed good agreement with the Kd determined by saturation analysis (390 pM vs. 682 pM, respectively). Inhibition of 0.3 nM [125I]-SCH 23982 binding by a series of dopaminergic antagonists verified the D1 nature of this binding site, exhibiting appropriate affinities and rank order of potency. The competition curves of all antagonists exhibited Hill coefficients that were not significantly different from 1. Inhibition of [125I]-SCH 23982 binding by dopamine and other dopaminergic agonists revealed the presence of high and low affinity agonist binding sites. Addition of 200 microM GppNHp effected a complete conversion of high affinity dopamine binding sites to a homogeneous population of low affinity dopamine sites. The D1 receptors identified in the parathyroid gland with [125I]-SCH 23982 appear to be pharmacologically identical with those previously characterized in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of dopamine in the maintenance and breakdown of D1/D2 synergism

The neurochemical factors involved in the maintenance and breakdown of dopamine D₁/D₂ receptor synergism were investigated by giving rats various pharmacological treatments that diminish the ability of dopamine to interact with its D₁ and/or D₂ receptors. Following these treatments, rats were observed for the expression of stereotyped motor behavior in response to independent stimulation of D₁ or D₂ receptors. Independent D₂-mediated responses were observed: (a) 2 h after the last of three daily reserpine (1 mg/kg) injections, (b) 48 h after bilateral 6-hydroxydopamine (6-OHDA) lesions of the mesostriatal pathways, (c) 24 h after a concentrated 48-h regimen (one injection/6 h) of eticlopride (0.5 mg/kg) or eticlopride + SCH 23390 (0.5 mg each), and (d) 2 h after a concentrated 48-h regimen (one injection/6 h) of α-methyl-p-tyrosine (αMPT; 100 mg/kg), but not after control treatments or a concentrated regimen of SCH 23390 alone. By contrast, independent D₁-mediated responses were observed only after three daily reserpine injections or 48 h after bilateral 6-OHDA lesions. Independent D₁-mediated stereotypy was not observed under control conditions or following a concentrated 48-h regimen of (a) SCH 23390 or eticlopride (0.5 mg/kg each) alone or in combination, (b) a high dose of SCH 23390 (1.0 mg/kg), (c) αMPT (100 mg/kg), or (d) αMPT (100 mg/kg)+SCH 23390 (1.0 mg/kg). Reserpine, bilateral 6-OHDA, and αMPT treatments produced striatal dopamine depletions of 96%, 92%, and 71%, respectively. These data indicate that the breakdown in D₁/D₂ synergism consists of two components: (a) D₁ independence from the controlling influence of D₂ receptors, and (b) D₂ independence from the controlling influence of D₁ receptors. The interaction of synaptic DA with its D₂ receptors plays a major role in determining whether these receptors can function independently of D₁ receptors, whereas reduced DA-D₁ activity alone appears insufficient to elicit D₁ independence.     

Decreased densities of dopamine D1 receptors in the putamen and hippocampus in senile dementia of the Alzheimer type

The density and distribution of dopamine D1 receptors as labeled with [3H]SCH 23390 was analyzed in post-mortem brain tissue from patients with senile dementia of the Alzheimer type (SDAT) and in controls using quantitative autoradiography. In SDAT patients D1 receptor densities were markedly decreased in parts of the hippocampus, with reductions of up to 89% compared to the control values in the molecular layer of the dentate gyrus, 57% in the strata oriens and pyramidalis of the CA1 and 74% in the CA3 subfields. Significant decreases in D1 receptors were also observed in the putamen (23%) but not in the caudate and substantia nigra. A slight but not significant decrease of D1 binding was observed in most external layers of the temporal and occipital cortices.     

Blockade of dopamine D1 receptors by SCH 23390 antagonizes discriminative stimulus effects of pentazocine

The purpose of this investigation was to test the hypothesis that the discriminative stimulus properties of pentazocine are mediated through an interaction with dopamine receptors. Rats were trained to discriminate s.c. injections of pentazocine (3.0 mg/kg) from vehicle in a two-choice discrete trial avoidance paradigm. SCH 23390 (0.003–0.056 mg/kg), a selective antagonist of dopamine D₁ receptors, inhibited the discriminative stimulus effects of pentazocine in a dose-dependent fashion, whilst the selective D₂ receptor antagonist sulpiride (20.0–80.0 mg/kg) did not antagonize them. It appears that the dopamine D₁ receptors play an important role in the discriminative stimulus effects of pentazocine.     

Modulation of dopamine metabolism in the retina via dopamine D2 receptors

When rats are placed in a lighted environment from the dark retinal DOPAC increases. There is no significant change of retinal dopamine (DA) under either lighting condition. Blockade of aromaticl-amino acid decar☐ylase results in a more rapid accumulation of DOPA in the retina of animals in the light than in the dark implying that DA synthesis and metabolism are more rapid in the light than in the dark. Retinal DOPAC increases in the dark and in the light when rats are treated with the DA D₂ antagonists sulpiride and spiperone. Treatment with the D₂ agonist, quinpirole, lowers the content of DA in the retina of rats kept in the dark or exposed to light. D₁ receptor drugs induce only limited changes in DA metabolism. We conclude that D₂ receptors play a principal role for modulating DA synthesis and metabolism in the rat retina.     

Radioimmunoligand characterization and immunohistochemical localization of dopamine D2 receptors on rods in the rat retina

The retinal neurotransmitter dopamine (DA), elaborated from intrinsic dopaminergic neurons as amacrine and interplexiform cells, is known to modulate several complex functions mediated by D₁ and D₂ receptors in the vertebrate retina. In this paper, we characterized and localized DA receptors of the D₂ family on rod outer segments (ROS) of the rat retina by a radioimmunoligand binding assay and by immunohistochemistry. Anti-anti-DA conjugated antibodies (or anti-idiotypic antibodies Ab₂) with used as ligand; BSA-glutaraldehyde-conjugated spiperone, eticlopride (D₂ antagonists) and DA were used as displacers. The linear Scatchard transformation indicated that data were best fit to the one-site model. By using the peroxidase-antiperoxidase technique, an intense labeling was located on rods. These results supported the paracrine action of DA on the photoreceptor cell.     

The effects of chronic continuous versus intermittent levodopa treatments on striatal and extrastriatal D1 and D2 dopamine receptors and dopamine uptake sites in the 6-hydroxydopamine lesioned rat — an autoradiographic study

The effects of chronic ‘continuous’ infusion and ‘intermittent’ modes of levodopa/carbidopa administration on apomorphine induced circling behaviour, DA uptake sites (labelled with [³H]mazindol) and D₁ and D₂ DA receptor binding (labelled with [³H]SCH 23390 and [³H]sulpiride, respectively) were investigated in rats with unilateral 6-OHDA lesions of the medial forebrain bundle. The circling behaviour in response to apomorphine was greatly enhanced following chronic ‘intermittent’ but not ‘continuous’ levodopa treatments. Following the ‘intermittent’ regime, the lower dose of apomorphine induced a period of intense circling with delayed onset and rapid offset, than in rats given either ‘continuous’ infusion of levodopa or saline. The 6-OHDA lesion itself induced gross depletion of [³H]mazindol binding in all striatal subregions, NAc and OT, but not frontal cortex. [³H]Sulpiride binding in the ventrolateral striatal quadrant was increased on the denervated side and this correlated with the peak contralateral turns in response to 0.5 mg/kg apomorphine challenge. This asymmetry in striatal [³H]sulpiride binding was reduced in both groups of rats receiving levodopa. [³H]sulpiride binding in the NAc and OT and [³H]SCH 23390 binding in the striatum, NAc, OT and SNr were unaffected by DA denervation or either regime of levodopa treatments. ‘Continuous’ infusion and not ‘intermittent’ injections of levodopa reduced [³H]mazindol binding in the striatal subregions and the frontal cortex on both the denervated and intact sides. The potentiation of the behavioural response to apomorphine by chronic ‘intermittent’ levodopa treatment does not correspond with the levodopa induced alterations in striatal or extrastriatal DA receptors. In the same group of animals the narrowing of the duration of response to the lower dose of apomorphine may mimic the fluctuations in response to levodopa, seen clinically in long-term levodopa treated parkinsonian patients.     

Synergistic effects of D1 and D2 dopamine agonists on turning behaviour in rats

In rats with unilateral 6-hydroxydopamine lesions of the substantia nigra, a specific D1 dopamine receptor agonist, SKF 38393A, at a dose that does not itself produce turning, significantly increased the contralateral rotation observed following a low dose of the specific D2 agonist LY 171555. Doses of SKF 38393A or the D2 agonist bromocriptine, which would themselves not induce turning, in combination produced a high rate of turning. These results suggest a synergistic interaction between D1 and D2 dopamine receptors in this system.     

Dopamine D2 receptor agents, but not dopamine D1, modify brain glucose metabolism

The effects of recently described selective dopamine D₁ and D₂ agonists and antagonists on brain glucose metabolism were studied using the 2-[¹⁴C]deoxyglucose autoradiographic technique. The administration of LY-141865 or YM-09151-2, which behave as a specific D₂ agonist and antagonist respectively, modified brain glucose metabolism in a manner similar to that previously described for more classical dopaminergic agents, such as apomorphine and haloperidol. In contrast, the administration of SKF 38393 or SCH 23390, a specific D₁ agonist and antagonist respectively, was not followed by significant modifications of brain glucose metabolism in any of the brain regions studied. These results indicate that D₂ but not D₁ dopamine receptors are involved in the regulation of local brain glucose metabolism.