pH dependence of ligand binding to D2 dopamine receptors

The binding of a range of ligands to D2 dopamine receptors in bovine caudate nucleus and recombinant CHO cells expressing the receptor has been determined at different pH values between 4.5 and 8.5. The maximum number of D2 dopamine receptor binding sites in each tissue was not affected by the change in pH, but the affinity of ligands for binding to the receptors was decreased as the pH was decreased. For classical dopamine antagonists, e.g. spiperone and haloperidol, the data on pH dependence of the dissociation constant for receptor binding indicated that the protonation of a single ionizing group on the receptor (pKa approximately 6) influenced the binding process. For antagonists of the substituted benzamide class, the data indicated that the protonation of two ionizing groups (pKa between 6 and 7) influenced the ligand binding process. These ionizing residues may correspond to Asp 114 for the classical antagonists and Asp 114 and Asp 80 for the substituted benzamide antagonists. Further evidence for the participation of carboxyl residues in the ligand binding process was obtained from the inhibition by N,N'-dicyclohexylcarbodiimide of the binding of [3H]spiperone and [3H]YM 09151-2 to D2 receptors in the recombinant CHO cells.     

Spare receptors and intrinsic activity: studies with D1 dopamine receptor agonists

Anti-nitric oxide synthase antibody was used to study the distribution, cytoarchitecture, and synaptic relations of nitric oxide synthase-like immunoreactive neurons in the whole rostral-caudal length of the dorsal raphe nucleus of the rat and compared them with serotonergic neurons. Results showed that the distribution of the nitric oxide synthase in the dorsal raphe nucleus was similar to that of the serotonergic neurons at the rostral part of the dorsal raphe nucleus, including the mediodorsal and the medioventral cell groups, and changed at the middle and caudal parts of the dorsal raphe nucleus. The cytoarchitecture of the nitric oxide synthase-like immunoreactive neurons in the medioventral cell group of the dorsal raphe nucleus was similar to that of the serotonergic neurons. Similar to the serotonergic neurons there, nitric oxide synthase-like immunoreactive neurons also received synapses from axon terminals that contained round, or flattened vesicles, or both kinds. Different to the serotonergic neurons, the few nitric oxide synthase-like immunoreactive axon terminals that were in this area formed synapses.     

Visualization of D1 dopamine receptors on living nucleus accumbens neurons and their colocalization with D2 receptors

To examine the substrate for dopamine (DA) synaptic action in the nucleus accumbens (nAcc), we visualized the cellular and subcellular distribution of DA receptors on postnatal nAcc neurons in culture using fluoroprobe derivatives of DA receptor ligands. Previously, we have shown that rhodamine-N-(p-aminophenethyl)-spiperone (NAPS) (10 nM), a derivative of the D2 antagonist spiperone, labels D2-like receptors on living nAcc neurons. We now show that rhodamine-Sch-23390 (30 nM), a derivative of the D1 antagonist, labels D1-like receptors. Putative specific membrane labeling reached a plateau after about 20 min. Labeling was stereospecific, as it was unaffected by competition with (-)-butaclamol, but blocked with (+)-butaclamol. We found that 52 +/- 7% of nAcc medium-sized neurons showed D1 labeling, which extended onto the dendrites. Labeling was also seen on presynaptic terminals, often abutting D1-positive and D1-negative cell bodies, consistent with a presynaptic modulatory role for D1 receptors. Larger neurons, which may be GABAergic or cholinergic interneurons, were also labeled. By sequential labeling first with rhodamine-Sch-23390 and then rhodamine-NAPS, we found that 38 +/- 6% of medium-sized neurons express both D1- and D2-like receptors, indicating that D1-D2 interactions may occur at the level of single postsynaptic neurons.     

Behavioural sensitization of mesolimbic dopamine D2 receptors in chronic fluoxetine-treated rats

A common action of chronic antidepressant treatments is the potentiation of dopaminergic transmission in the limbic system. We now report that chronic, but not acute, treatment with fluoxetine (2.5 mg/kg by intragastric gavage once a day for 21 days) potentiates the locomotor stimulant effect of quinpirole, a selective dopamine D2/D3 receptor agonist. However, neither quinpirole-induced stereotypies nor the sedative effects elicited by low doses of this dopamine receptor agonist are influenced by chronic fluoxetine. These results suggest that fluoxetine, as well as classical antidepressants, sensitize postsynaptic dopamine D2/D3 receptors in the mesolimbic system.     

Agonist action at D2(long) dopamine receptors: ligand binding and functional assays

Clinical pathways are being introduced by hospitals to reduce costs and control unnecessary variation in care. We studied 766 inpatients to measure the impact of a perioperative clinical pathway for patients undergoing knee replacement surgery on hospital costs. One hundred twenty patients underwent knee replacement surgery before the development of a perioperative clinical pathway, and 63 patients underwent knee replacement surgery after pathway implementation. As control groups, we contemporaneously studied 332 patients undergoing radical prostatectomy (no clinical pathway in place for these patients) and 251 patients undergoing hip replacement surgery without a clinical pathway (no clinical pathway and same surgeons as patients having knee replacement surgery). Total hospitalization costs (not charges), excluding professional fees, were computed for all patients. Mean (+/-SD) hospital costs for knee replacement surgery decreased from $21,709 +/- $5985 to $17,618 +/- $3152 after implementation of the clinical pathway. The percent decrease in hospitalization costs was 1.56-fold greater (95% confidence interval 1.02-2.28) in the knee replacement patients than in the radical prostatectomy patients and 2.02-fold greater (95% confidence interval 1.13-5.22) than in the hip replacement patients. If patient outcomes (e.g., patient satisfaction) remain constant with clinical pathways, clinical pathways may be a useful tool for incremental improvements in the cost of perioperative care. Implications: Doctors and nurses can proactively organize and record the elements of hospital care results in a clinical pathway, also known as "care pathways" or "critical pathways." We found that implementing a clinical pathway for patients undergoing knee replacement surgery reduced the hospitalization costs of this surgery.     

Photoaffinity labeling of D1 and D5 dopamine receptors

Although human D1 and D5 dopamine receptors are encoded by distinct genes and share only 50% sequence homology at the amino acid level, their pharmacological properties are identical. Using a selective D1 receptor photoaffinity radioligand, (+/-)-7-[125I]iodo-8-hydroxy-3-methyl-1-(4-azidophenyl)-2,3,4,5-tetrahyd ro-1H-3-benzazepine ([125I]MAB), we have further probed the molecular properties of these receptors in transfected GH4C1 rat pituitary cells. Under reversible, non-covalent binding conditions, [125I]MAB bound to both the D1 and the D5 receptors with identical affinities, dopaminergic selectivity and stereospecificity. Upon photoactivation of the bound [125I]MAB, the label was incorporated into a approximately 64,000 mol. wt protein corresponding to the D1 dopamine receptor. However, there was no specific photoincorporation of the ligand observed in D5 receptors. The lack of [125I]MAB photolabeling of D5 receptors was independent of the cell line chosen, since similar results were obtained using other transfected cells. The data suggest that although both D1 and D5 receptors share structurally similar binding sites, the protein domains around the sites are different. Thus, although there are currently no specific compounds which bind preferentially to D1 or D5 receptors, these receptors can be distinguished from one another by the inability of [125I]MAB to photolabel D5, but not D1, receptors. Such selective targeting of a specific receptor may be useful in understanding the functional importance and/or interaction between closely related members of the same receptor family when co-expressed in the same cell.     

Opposing roles for dopamine D1 and D2 receptors in the regulation of hypothalamic tuberoinfundibular dopamine neurons

The purpose of the present study was to characterize pharmacologically dopamine D1 receptor-mediated inhibition of tuberoinfundibular dopamine neurons in males rats, and to determine if inhibitory dopamine D1 receptors oppose stimulatory dopamine D2 receptors and account for the inability of mixed dopamine receptor agonists to alter the activity of these neurons. Tuberoinfundibular dopamine neuronal activity was estimated by measuring the concentrations of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence, the region of the hypothalamus containing terminals of these neurons. Administration of the dopamine D1 receptor agonist (+/-)-1 phenyl-2,3,4,5-tetrahydro-(1 H)-3-benzazepine-7,8-diol (SKF38393) decreased median eminence DOPAC and increased plasma prolactin concentrations, whereas administration of the dopamine D1 receptor antagonist ((-)-trans,6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo[d]naphtho-[2,1 b]azepine (SCH39166) increased median eminence DOPAC concentrations but had not effect on plasma prolactin. The inhibitory effect of SKF38393 on median eminence DOPAC concentrations was blocked by SCH39166. These results demonstrate that acute activation of dopamine D1 receptors inhibits the activity of tuberoinfundibular dopamine neurons and thereby increases prolactin secretion, and that under basal conditions dopamine D1 receptor-mediated inhibition of tuberoinfundibular dopamine neurons is tonically active. Administration of the dopamine D2 receptor agonist (5aR-trans)-5,5a,6,7,8,9,9a,10-octahydro-6-propyl-pyridol[2, 3-g]quinazolin-2-amine (quinelorane) increased median eminence DOPAC concentrations, and SKF38393 caused a dose-dependent reversal of this effect. Administration of the mixed dopamine D1/D2 receptor agonist R(-)-10,11-dihydroxy-apomorphine (apomorphine) had no effect per se, but blocked quinelorane-induced increases in DOPAC concentrations in the median eminence. These results reveal that concurrent activation of dopamine D1 and D2 receptors nullifies the actions of each of these receptors on tuberoinfundibular dopamine neurons, which likely accounts for the lack of an acute effect of mixed dopamine D1/D2 receptor agonists on these hypothalamic dopamine neurons.     

In vivo studies on striatal dopamine D1 and D2 site binding in L-dopa-treated Parkinson's disease patients with and without dyskinesias

Dyskinesias are usually seen in Parkinson's disease (PD) patients after several years of L-dopa therapy. Their presence has been attributed to supersensitivity of striatal D1 and D2 receptors. We have used PET to assess striatal D2 receptor binding in untreated PD patients and striatal D1 and D2 binding in L-dopa-treated PD patients. Untreated patients showed a 14% increase in mean D2 receptor binding in the putamen contralateral to the more affected limbs (p < 0.02). Treated patients were segregated into subgroups according to the presence or absence of dyskinesias. There were no differences in mean caudate and putamen D1 and D2 binding between dyskinetic and nondyskinetic patients, matched for duration of clinical disease. Both dyskinetic and nondyskinetic PD subgroups showed a similar 16% reduction of mean caudate D2 binding (p < 0.01) with normal D2 binding in putamen. Mean caudate and putamen D1 binding potentials of both subgroups were reduced by 10% compared with those of controls, though this trend did not reach significance. Putamen D1 binding, however, showed a negative correlation with duration and L-dopa treatment (p < 0.03). These findings suggest that, while exposure of PD patients to L-dopa may be associated with reductions in caudate D2 and caudate and putamen D1 receptor, dyskinesias are unlikely to result from alterations in striatal dopamine receptor binding.     

D1 receptors mediate dopamine action in the fetal suprachiasmatic nuclei: studies of mice with targeted deletion of the D1 dopamine receptor gene

Studies in rodents suggest the presence of a dopaminergic system that influences the function of a biological clock in the hypothalamic suprachiasmatic nuclei (SCN). To provide insights into mechanisms of dopamine action in the SCN, we studied transgenic mice that had either one allele (+?-) or both alleles (-/-) of the D1 dopamine receptor gene deleted, along with normal (+/+) littermates. As expected, receptor labelling autoradiography studies using [125I]SCH 23982 showed a complete absence of D1 dopamine receptor binding sites in the SCN of -/- animals. When pregnant mice from +?- x +?- matings were injected with the D1 receptor agonist SKF 38393, or the dopamine reuptake blocker GBR 12909 at day 19 of gestation, c-fos mRNA expression was observed in the SCN of +/+ fetuses. In contrast, c-fos mRNA induction was not seen in -/- or +?- litter mates. Injection of cocaine into pregnant dams also resulted in robust SCN c-fos mRNA expression in +/+ mice. Increases in SCN c-fos mRNA expression were also seen in +?- and -/- mice suggesting that cocaine action in the SCN involves both D1 receptor-dependent and -independent mechanisms. Collectively, our studies of transgenic mice deficient in D1 receptors support the presence of a functional dopaminergic system in the fetal SCN. We also identify D1 receptors as the prominent transducer of dopamine action in the fetal SCN.     

Adenosine A2A receptors modulate the binding characteristics of dopamine D2 receptors in stably cotransfected fibroblast cells

In membrane preparations from rat striatum, where adenosine A2A and dopamine D2 receptors are coexpressed, stimulation of adenosine A2A receptors was found to decrease the affinity of dopamine D2 receptors for dopamine agonists. We now demonstrate the existence of this antagonistic interaction in a fibroblast cell line (Ltk-) stably transfected with the human dopamine D2 (long-form) receptor and the dog adenosine A2A receptor cDNAs (A2A-D2 cells). In A2A-D2 cells, but not in control cells only containing dopamine D2 receptors (D2 cells), the selective adenosine A2A agonist 2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethyl-carboxamido adenosine (CGS 21680) induced a 2-3-fold decrease in the affinity of dopamine D2 receptors for dopamine, as shown in competition experiments with dopamine versus the selective dopamine D2 antagonist [3H]raclopride. By contrast, activation of the constitutively expressed adenosine A2B receptors with 5'-N-ethyl-carboxamidoadenosine (NECA) did not modify dopamine D2 receptor binding. In A2A-D2 cells CGS 21680 failed to induce or induced only a small increase in adenosine-3',5'-cyclic-monophosphate (cAMP) accumulation. In D2 cells NECA- or forskolin-induced adenylyl cyclase activation was not associated with any change in dopamine D2 receptor binding. These results indicate that adenylyl cyclase activation is not involved in the adenosine A2A receptor-mediated modulation of the binding characteristics of the dopamine D2 (long-form) receptor.     

The time course of binding to striatal dopamine D2 receptors by the neuroleptic ziprasidone (CP-88,059-01) determined by positron emission tomography

Positron emission tomography (PET) and 11C-raclopride were used to assess the time course of binding to central dopamine D2 receptors by the novel neuroleptic ziprasidone. In a third party blind study, six healthy male control subjects received a predose of 40 mg ziprasidone and were scanned at an interval of between 4 and 36 h post-dose. One additional subject was assigned to placebo predose and was scanned at 4 h post-dose. Binding potential (BP) was compared with that seen in the subject predosed with placebo and with that seen in nine unmedicated normal volunteers. Subjects studied up to 12 h post-dose had BPs that were greater than 2 SD less than the mean BP, indicative of extensive D2 receptor binding by ziprasidone. With increasing time between dosing and PET scanning there was a curvilinear increase in BP, so that all studies performed at or after 18 h post-dose gave BPs in the normal range (mean +/- 2 SD). Elevated prolactin levels returned to within the normal range by 18 h post-dose. PET measures of binding potential correlated significantly with serum levels of ziprasidone at the time of scanning and less significantly with absolute prolactin levels at the same time.     

Left-right asymmetry of striatal dopamine D2 receptors

Brain functions may be lateralized to the right or the left hemisphere. However, the biochemical characteristics accompanying these functions are largely unknown. To test possible lateralization of striatal dopamine D2 receptors, we examined 18 volunteers using 123I-iodobenzamide and single photon emission tomography. The striatum-to-cerebellum D2 binding ratio was 1.93 +/- 0.22 (mean +/- S.D.) on the right side and 1.85 +/- 0.19 on the left side. In 14 subjects, D2 binding was higher in the right compared to the left striatum (P < 0.05). These results are supported by a meta-analysis performed on 15 studies reported in the literature. We conclude that side differences of striatal dopamine D2 receptors exist. We propose that motor activity could be responsible for our findings.     

Differential influence of D1 and D2 dopamine receptors on acute opiate withdrawal in guinea-pig isolated ileum

1. The effects exerted by D1 and D2 dopamine agonists and antagonists on the acute opiate withdrawal induced by mu- and kappa-receptor agonists were investigated in vitro. 2. Following a 4 min in vitro exposure to morphine (moderately selective mu-agonist), [D-Ala2, Me-Phe4, Gly-ol5]enkephalin (DAMGO, highly selective mu-agonist) or U-50488H (highly selective kappa-agonist) the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. 3. The non-selective dopamine receptor antagonist haloperidol when added before or after the opioid agonists, was able dose-dependently to prevent or to reverse the naloxone-induced contracture after exposure to mu- (morphine and DAMGO) and kappa- (U-50488H) opioid agonists. The non-selective dopamine receptor agonist, apomorphine, was able to exert the same effects only at the highest concentration used. 4. The selective D2 dopamine receptor antagonist, sulpiride, was also able to reduce dose-dependently both mu- and kappa-opioid withdrawal, whereas the D1-receptor selective antagonist SCH 23390 did not affect either mu- or kappa-opioid withdrawal. 5. Bromocriptine, a D2 selective dopamine receptor agonist was able to increase significantly, and in a concentration-dependent manner, the naloxone-induced contracture by mu- and kappa-opioid agonists, whereas SKF 38393, a D1 selective dopamine receptor agonist, increased only the withdrawal after morphine or U50-488H. 6. Our data indicate that both D1 and D2 dopamine agonists and antagonists are able to influence opiate withdrawal in vitro, suggesting an important functional interaction between the dopaminergic system and opioid withdrawal at both the mu- and kappa-receptor level. 7. Furthermore, the ability of sulpiride to block strongly opiate withdrawal when compared to SCH 23390, as well as the effect of bromocriptine to increase opiate withdrawal suggest that D2 dopamine receptors may be primarily involved in the control of opiate withdrawal.     

Role of dopamine D1 and D2 receptors in the nucleus accumbens in mediating reward

The objectives of this study were to examine the involvement of D1 and D2 receptors within the nucleus accumbens (ACB) in mediating reinforcement. The intracranial self-administration (ICSA) of D1 and D2 agonists was used to determine whether activating D1 and/or D2 receptors within the ACB of Wistar rats is reinforcing. At concentrations of 0.25, 0.50, and 1.0 mM (25, 50, and 100 pmol/100 nl of infusion), neither the D1 agonist R(+)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol [SKF 38393 (SKF)] hydrochloride nor the D2 agonist (-)-quinpirole (Quin) hydrochloride was self-administered into the shell region of the ACB. On the other hand, equimolar mixtures of SKF and Quin (SKF+Quin), at concentrations of 0.25, 0.50, and 1.0 mM each, were significantly self-infused into the ACB shell. The core region of the ACB did not support the ICSA of SKF+Quin at any of these concentrations. Rats increased lever pressing when the response requirement was increased from a fixed ratio 1 (FR1) to FR3, and they responded significantly more on the infusion lever than they did on the control lever. Coadministration of either 0.50 mM R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine (SCH 23390) hydrochloride, a D1 antagonist, or 0.50 mM S(-)-sulpiride, a D2 antagonist, completely abolished the ICSA of the mixture of SKF+Quin (each at 0.50 mM) into the ACB shell. The present results suggest that concurrent activation of D1- and D2-type receptors in the shell of the ACB had a cooperative effect on DA-mediated reward processes.     

The effects of anandamide on memory consolidation in mice involve both D1 and D2 dopamine receptors

Post-training administration of anandamide (1.5, 3, 6 mg/kg) dose-dependently impairs the retention of an inhibitory avoidance response in mice. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation, as they were observed when drugs were given at short, but not long, periods of time after training, i.e. when the memory trace was susceptible to modulation. Pretreatment with either selective D1 or D2 dopamine (DA) receptor agonists, SKF 38393 and quinpirole, at doses that were ineffective when given alone (5 and 0.25 mg/kg, respectively), antagonized the effects of anandamide on memory consolidation, suggesting that D1 and D2 receptors are similarly involved in the effects of anandamide on memory consolidation. These results are discussed in terms of a possible inverse relationship between the modulation of memory processes by endogenous cannabinoid and DA systems.     

D1 dopamine receptor binding and mRNA levels are not altered after neonatal 6-hydroxydopamine treatment: evidence against dopamine-mediated induction of D1 dopamine receptors during postnatal development

The role of dopaminergic innervation on the postnatal developmental expression of D1 dopamine receptors was investigated. Bilateral destruction of dopamine-containing neurons was achieved by treating rats intracisternally with 6-hydroxydopamine (6-OHDA) on postnatal day 3, and rats were killed on day 21. To ensure effective reduction of D1 receptor activation by residual dopamine, a group of 6-OHDA-lesioned rats was given twice daily injections of the D1 receptor antagonist SCH-23390, from day 4 to 20. D1 dopamine receptor binding was assessed in the caudate-putamen, nucleus accumbens, and olfactory tubercle by quantitative autoradiographic analysis of [3H]SCH-23390 binding. In addition, the relative amount of D1A receptor mRNA was assessed by in situ hybridization of a 35S-labeled riboprobe. In the developing rats, neither the amount of [3H]SCH-23390 binding nor the amount of D1A receptor mRNA was altered by 6-OHDA lesioning followed by chronic treatment with SCH-23390. Thus, bilateral destruction of dopamine-containing neurons and treatment with SCH-23390 in neonatal rats did not interfere with the developmental expression of D1 receptors or alter the levels of mRNA that code for this receptor protein. Treatment of intact rats with SCH-23390 from postnatal day 4 to 20 also did not alter [3H]SCH-23390 binding or levels of D1 receptor mRNA. However, adult rats treated chronically with SCH-23390 exhibited increased [3H]SCH-23390 binding but did not show a significant change in D1 receptor mRNA levels.     

Chronic dopamine D1, dopamine D2 and combined dopamine D1 and D2 antagonist treatment in Cebus apella monkeys: antiamphetamine effects and extrapyramidal side effects

STUDY DESIGN: This study involved weekly radiographic examination of pinealectomized rats, hamsters, and chickens to observe the development of scoliosis. OBJECTIVES: To determine whether pinealectomy produces scoliosis in animals more closely related phylogenetically to humans than to chickens, namely rats and hamsters, which are representative of mammals. SUMMARY OF BACKGROUND DATA: Pinealectomy in 3-day-old chickens has consistently resulted in the development of scoliosis with many characteristics similar to those seen in patients with adolescent idiopathic scoliosis. It has not been determined whether this phenomenon is restricted solely to chickens or is applicable to other animals, especially those more closely related to humans. METHODS: The pineal gland was removed from young rats, hamsters, and chickens. All animals underwent radiography weekly to detect the development of any scoliosis. Weight and length measurements were also taken weekly, and serum melatonin levels were determined at the time the animals were killed. RESULTS: Scoliosis was not observed in either the rats or the hamsters. In contrast, scoliosis developed in 10 of 21 chickens. Serum melatonin levels in all pinealectomized animals were zero. CONCLUSIONS: In contrast to the chickens, pinealectomy does not seem to cause scoliosis in either young rats or hamsters. The reasons for this discrepancy may include differences in the physiology and spinal morphology of the rat and hamster in comparison with the chicken. In the pinealectomized chickens, the results also suggest that future scoliosis development might be indicated by a significant increase in size when they are compared with pinealectomized chickens that do not develop scoliosis. Such differences in growth rates also distinguish patients with adolescent idiopathic scoliosis.     

The roles of accumbal dopamine D1 and D2 receptors in maternal memory in rats.

Female rats show enhanced maternal responsiveness toward their young if they have had maternal experiences before. This kind of maternal experience-based memory is critically dependent on the mesolimbic dopamine (DA) system, especially the nucleus accumbens (NA) shell. However, the relative contributions of the two main DA receptor systems (D? and D?) within the shell have not been delineated. This study investigates the roles of dopamine D? and D? receptors in maternal memory by infusing a selective D? antagonist, SCH-23390; a selective D? antagonist, sulpiride; or a combination D?/D? antagonist, cis-Z-flupenthixol, into the NA shell of postpartum female rats. Sulpiride-infused rats showed a significantly longer latency to exhibit full maternal behavior following a 10-day pup isolation period in comparison to the controls that received a vehicle. Cis-Z-flupenthixol disrupted maternal memory to a greater extent, as rats receiving this showed the longest latencies to express maternal behavior. SCH-23390 infusions had only marginal effects. These findings suggest that both the D? and the D? receptor subtypes play a role in the consolidation of maternal memory and they might do so by mediating the motivational salience of pup stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Heterogeneous distributions of histamine H3, dopamine D1 and D2 receptors in rat brain

The changes of the histamine H3 and dopamine D1 or D2 receptor binding sites induced by quinolinic acid treatment were studied in order to discriminate the comparative distribution. This treatment resulted in similar decreases in histamine H3 and dopamine D1 receptor binding sites in the striatum and ipsilateral substantia nigra. Dopamine D2 receptor binding sites were relatively well conserved, whereas H3 receptors decreased considerably. These results suggest that histamine H3 and dopamine D1 receptor binding sites are localized on the striatonigral projection neurones which are together sensitive to quinolinic acid, and that the distributional compartment of dopamine D2 receptor binding sites is quite different from those of histamine H3 and dopamine D1 receptors.