ergoline and eticlopride

Dopamine (DA) D1- and D2-agonists and antagonists were administered at fixed doses to assess putative dopaminergic involvement in timing behavior in rats performing under a peak-interval schedule. Significant shifts in response distributions to the left (consistent with the overestimation of the passage of time) were observed after treatment with the D1- and D2-agonists SKF 38393 and quinpirole, respectively. Both DA antagonists, eticlopride (D2) and SCH 23390 (D1), shifted the response distributions to the right (consistent with the underestimation of the passage of time), but neither drug produced statistically significant shifts. Based on percent shift in peak time from predrug baseline values, no significant differences were detected between agents as a function of their reported affinities for the D1- or D2-receptors. Results indicate the need for a systematic evaluation of each drug at various doses and a more detailed examination of the use of temporal schedules in predicting the efficacy of psychotherapeutic agents.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Benzazepines; Conditioning, Operant; Dopamine Agonists; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Ergolines; Male; Psychomotor Performance; Quinpirole; Rats; Receptors, Dopamine D1; Receptors, Dopamine D2; Reinforcement Schedule; Salicylamides; Time Factors

Many aspects of retinal physiology are controlled by a circadian clock including at least two steps in the melatonin synthetic pathway: the activity of the enzyme, N-acetyltransferase (NAT), and mRNA levels of the rate-limiting enzyme trytophan hydroxylase (TPH). Light and dopamine (through D2-like dopamine receptors) can phase shift the clock, and can also acutely inhibit NAT activity, resulting in supressed melatonin synthesis. In this paper, we show that eyecups cultured in constant darkness maintain a clock-controlled rhythm in TPH mRNA, with low levels in early day, rising to a peak in early night. Both eyecups and isolated retinas, cultured in light during the day, also exhibit a similar increase in TPH mRNA levels, indicating that this expression is not acutely inhibited by light. Treatment with light or quinpirole (D2 dopamine receptor agonist) in early night, at a time and dose that acutely inhibits NAT activity, does not change levels of TPH mRNA. Addition of eticlopride (D2 dopamine receptor antagonist) during the day, also has no effect on the normal daytime increase in TPH message levels. Therefore, TPH mRNA level is controlled by a circadian clock located within the eye, but acute effects of light or dopamine are not detected.

Topics: Animals; Cells, Cultured; Circadian Rhythm; Dopamine Agonists; Dopamine Antagonists; Ergolines; Gene Expression Regulation; Photoperiod; Quinpirole; Retina; RNA, Messenger; Salicylamides; Tryptophan Hydroxylase; Xenopus laevis

Repeated treatment with the non-selective dopamine agonist apomorphine results in behavioral sensitization and enhanced dopamine synthesis in dopamine projection fields. To examine the role of D2-type dopamine receptors in modulating these effects, the present experiment assessed the effects of repeated treatment with the D2-type agonist quinpirole on locomotor activity and dopamine synthesis. In the first experiment, rats were treated with vehicle or one of two doses (0.3 or 3.0 mg/kg) of quinpirole for 8 days. Daily measures of locomotor activity revealed an initial suppression of activity produced by quinpirole which dissipated over the 8 days of treatment. A trend for an increase in activity for 3.0 mg/kg quinpirole compared to vehicle was obtained on day 8. Twenty-four hours after cessation of treatment, dopamine synthesis, measured as accumulation of 3,4-dihydroxyphenylalanine (DOPA) after treatment with the DOPA decarboxylase inhibitor NSD-1015, was enhanced in the striatum, but not nucleus accumbens-olfactory tubercle (NAOT) or ventral mesencephalon (VM). In Experiment 2, rats were treated for 8 days with vehicle, 3.0 mg/kg quinpirole or the D1 antagonist SCH 23390 (0.5 mg/kg) in a two (vehicle or quinpirole) x two (vehicle or SCH 23390) design. Quinpirole-alone treatment resulted in a reduction of the locomotor suppressant effects of the drug. SCH 23390-alone and quinpirole-SCH 23390 combined treatment resulted in decreased activity compared to the vehicle control group that did not change across days. DOPA accumulation was enhanced in the striatum and NAOT after quinpirole treatment; however, SCH 23390 had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Benzazepines; Dihydroxyphenylalanine; Dopamine; Dopamine Agonists; Dopamine Antagonists; Ergolines; Male; Motor Activity; Neostriatum; Nucleus Accumbens; Quinpirole; Rats; Rats, Wistar; Salicylamides

The D2 dopamine agonist, bromocriptine, has been used as treatment for human PRL-secreting pituitary adenomas. The result of bromocriptine treatment is often a substantial reduction of tumor mass, suggesting that the dopamine agonist is acting as an antiproliferative agent. This action can be observed with a clonal pituitary tumor cell line. The agonist activation of the D2 dopamine receptor inhibits the growth of GH4ZR7 cells, a GH4C1 cell line stably transfected with the cDNA encoding the short form of the D2 dopamine receptor. This effect of dopamine was not sensitive to overnight treatment with 100 ng/ml pertussis toxin. Treatment of GH4ZR7 cells with the phorbol ester 4 beta-phorbol 12,13-didecanoate resulted in the loss of dopaminergic inhibition of growth, whereas treatment with 4 alpha-phorbol 12,13-didecanoate had no effect. Inhibitors of protein kinase-C (PKC), such as staurosporine and H7, also blocked the effect of dopamine. Down-regulation of cellular PKC by phorbol ester treatment resulted in a complete loss of dopaminergic inhibition of growth. Long term treatment of GH4ZR7 cells with TRH results in a specific down-regulation of the epsilon form of PKC and abolished the ability of dopamine to inhibit growth. These results suggest that PKC epsilon is involved in mediating the antiproliferative effects of dopamine. This mediation of growth appears to be through a novel signaling pathway for the D2 dopamine receptor.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Alprenolol; Animals; Apomorphine; Benzazepines; Butaclamol; Carcinogens; Cell Division; Cell Line; DNA; Dopamine; Ergolines; Humans; Isoenzymes; Kinetics; Norepinephrine; Pertussis Toxin; Phorbol Esters; Pituitary Neoplasms; Protein Kinase C; Quinpirole; Receptors, Dopamine D2; Salicylamides; Spiperone; Thymidine; Transfection; Tumor Cells, Cultured; Virulence Factors, Bordetella

1. The effects of selective dopamine receptor compounds on the spontaneous activity of single neostriatal neurons were examined extracellularly. 2. Intravenous administration of quinpirole, the D2 agonist, elicited a dose-dependent depression in discharge rate. 3. Quinpirole-evoked depression was reversed by the D2 antagonist eticlopride, but not the D1 antagonist SCH 23390. 4. The partial D1 agonist, SKF 38393 induced depression and excitation in equal proportion. 5. A dose of 0.25 mg/kg SCH 23390 blocked SKF 38393-induced depression but not excitation. 6. SKF 38393-induced excitation was antagonized by eticlopride and in some cases by a higher dose of SCH 23390.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Benzazepines; Depression, Chemical; Dopamine Agonists; Dopamine Antagonists; Ergolines; Male; Neostriatum; Neurons; Quinpirole; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, Dopamine D2; Salicylamides

Molecular cloning studies have defined a family of dopamine D2-like receptors (D2, D3, and D4), which are the products of separate genes. Our previous work has shown that stimulation of dopamine D2-like receptors in cultures of fetal cortical neurons increases the extension and branching of neurites. To determine which D2-like receptors possess morphogenic potentials, a clonal mesencephalic cell line (MN9D) was transfected with D2, D3, or D4 receptor subtypes and treated with quinpirole, an agonist of D2-like receptors, and changes in morphological characteristics were quantitated. Stimulation of D2 receptors increased the number and branching of neurites with little effect on neurite extension; stimulation of D3 and D4 receptors increased the branching and extension of neurites. Similar results were found for primary mesencephalic cultures stimulated with quinpirole. These results suggest that the known D2-like receptors have specific developmental roles in regulating neuronal morphogenesis of dopaminergic pathways.

Topics: Animals; Cell Line; Dopamine Agents; Ergolines; Humans; Mesencephalon; Neurites; Neurons; Quinpirole; Rats; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Dopamine D4; Salicylamides; Transfection

The mechanism of action for the behavioral stimulant effects of caffeine has been extensively studied, but results have been ambiguous and inconsistent. The present study examined the role of dopamine in caffeine-induced stimulation of locomotor activity in rats. d-Amphetamine was also tested for comparison. Locomotor activity of male Sprague-Dawley rats (300-350 g) was measured using two-channel electronic activity monitors. Activity counts were recorded for 30 min following a 30-min pretreatment with either caffeine (3.0-100 mg/kg, IP) or d-amphetamine (0.1-3.0 mg/kg, IP) alone and in combination with the D1 dopamine antagonist SCH23390 (0.01 and 0.003 mg/kg, SC) or the D2 dopamine antagonists sulpiride (30 mg/kg, SC) or eticlopride (0.03 mg/kg, SC). Caffeine and d-amphetamine dose dependently increased locomotor activity. This effect of both caffeine and d-amphetamine was blocked by SCH23390 as well as by eticlopride. Sulpiride blocked the stimulatory effects of caffeine but not d-amphetamine. These results suggest that the locomotor stimulant effect of caffeine, like that of d-amphetamine, is mediated through dopaminergic systems; both D1 and D2 receptors appear to be involved.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Caffeine; Dextroamphetamine; Dopamine Agents; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Ergolines; Male; Motor Activity; Quinpirole; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Salicylamides; Sulpiride

The human D4 dopamine receptor has been expressed in Sf9 insect cells where it appears to couple to endogenous G proteins. Increased guanine nucleotide exchange to G proteins is a reflection of receptor activation and can be followed using a [35S]GTP gamma S binding assay. By measuring D4 receptor stimulation of [35S]-GTP gamma S binding we have been able to characterize several dopaminergic compounds for their functional activity at this receptor. In Sf9 cells expressing the D4 receptor, dopamine, quinpirole, and dp-2-aminodihydroxy-1,2,3,4-tetrahydronaphthalene were all full agonists, whereas (-)-apomorphine appeared to be a partial agonist. No increase in [35S]GTP gamma S binding was observed for noninfected cells or cells infected with an unrelated sequence. The quinpirole-stimulated [35S]GTP gamma S binding could be inhibited by the antagonists clozapine, eticlopride, and haloperidol, and a Schild analysis of these data showed that all three compounds were acting as competitive antagonists of D4 receptors. The rank order of affinities derived from the Schild analysis correlated with that obtained from [3H]spiperone competition binding assays. In conclusion, we have shown that, using this assay system, it is possible to investigate functionally the pharmacology of a recombinant G protein-coupled receptor in the absence of any information regarding the eventual second messenger pathways involved.

Topics: Animals; Cell Line; Clozapine; DNA; Dopamine; Dopamine Agents; Ergolines; Guanosine 5'-O-(3-Thiotriphosphate); Haloperidol; Humans; Ligands; Moths; Quinpirole; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D4; Recombinant Proteins; Salicylamides; Spiperone; Sulfur Radioisotopes; Tritium

Many effects resulting from D2 dopamine (DA) receptor stimulation are manifest only when D1 DA receptors are stimulated by endogenous DA. When D1 receptor stimulation is enhanced by administration of selective D1 receptor agonists, the functional effects of selective D2 agonists are markedly increased. These qualitative and quantitative forms of D1/D2 DA receptor synergism are abolished by chronic DA depletion when both D1 and D2 DA receptors are supersensitive. Using both electrophysiological and behavioral methods, the present study examined the effects of selective D1 and D2 receptor supersensitivity, induced by repeated administration of selective D1 or D2 receptor antagonists, on the synergistic relationships between D1 and D2 receptors. Daily administration of the selective D2 antagonist eticlopride (0.5 mg/kg, s.c.) for 3 weeks produced a selective supersensitivity of both dorsal (caudate-putamen) and ventral (nucleus accumbens) striatal neurons to the inhibitory effects of the D2 agonist quinpirole (applied by microiontophoresis). This treatment also abolished the normal ability of the D1 agonist SKF 38393 to potentiate quinpirole-induced inhibition, and relieved D2 receptors from the necessity of D1 receptor stimulation by endogenous DA (enabling), as indicated by significant electrophysiological and behavioral (stereotypy) effects of quinpirole in eticlopride-pretreated, but not saline-pretreated, rats that were also acutely depleted of DA. Daily administration of the selective D1 receptor antagonist SCH 23390 (0.5 mg/kg, s.c.) caused supersensitivity of striatal neurons to the inhibitory effects of SKF 38393 and also abolished both the ability of SKF 38393 to potentiate quinpirole-induced inhibition and the necessity of D1 receptor stimulation for such inhibition. However, both quinpirole-induced inhibition of striatal cells and stereotyped responses were also somewhat enhanced in SCH 23390-pretreated rats. When such D1-sensitized rats were acutely depleted of DA, the behavioral effects of quinpirole were intermediate between saline-pretreated rats with acute DA depletion and SCH 23390-pretreated rats without acute DA depletion. Based upon these and related results, it is argued that the enhanced effects of quinpirole in D1-sensitized rats are due to a heterologous sensitization of D2 receptors rather than to enhanced enabling resulting from supersensitive D1 receptors. It is suggested that supersensitivity of either D1 or D2 receptors can lead

Topics: Animals; Behavior, Animal; Benzazepines; Corpus Striatum; Dopamine Agents; Dopamine D2 Receptor Antagonists; Electrophysiology; Ergolines; Male; Neurons; Quinpirole; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, Dopamine D2; Salicylamides; Stereotyped Behavior

Destruction of the substantia nigra produces striatal D1 dopamine receptor supersensitivity without increasing receptor number or affinity, thus implicating postreceptor mechanisms. The nature of these mechanisms is unknown. Increased striatal c-fos expression ipsilateral to a unilateral lesion of the substantia nigra in rats treated with appropriate dopamine agonists provides a cellular marker of D1 receptor supersensitivity. D1 receptors are positively linked to adenylate cyclase and therefore to cAMP-dependent protein kinase. Because expression of the c-fos gene in response to cAMP- and Ca2+/calmodulin-regulated protein kinases depends on phosphorylation of cAMP-response element-binding protein (CREB) at Ser-133, we examined CREB phosphorylation after dopaminergic stimulation in cultured striatal neurons and in the striatum of rats after unilateral 6-hydroxydopamine ablation of the substantia nigra. Using an antiserum specific for CREB phosphorylated at Ser-133, we found that dopamine increases CREB phosphorylation in cultured striatal neurons. This effect was blocked by a D1 antagonist. L-Dopa produced marked CREB phosphorylation in striatal neurons in rats ipsilateral, but not contralateral, to a 6-hydroxydopamine lesion. This response was blocked by a D1 antagonist, but not a D2 antagonist, and was reproduced by a D1 agonist, but not a D2 agonist. These findings are consistent with the hypothesis that D1 receptor supersensitivity is associated with upregulated activity of cAMP-dependent or Ca2+/calmodulin-dependent protein kinases, or both, following dopamine denervation of striatal neurons.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Benzazepines; Calcium-Calmodulin-Dependent Protein Kinases; Cells, Cultured; Corpus Striatum; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; Dopamine; Embryo, Mammalian; Ergolines; Gene Expression; Genes, fos; Levodopa; Male; Neurons; Oxidopamine; Phosphorylation; Quinpirole; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, Dopamine D2; Salicylamides; Substantia Nigra

D2-like dopamine receptors are thought to control presynaptic dopamine synthesis and release. Because these receptors comprise a family which includes D2, D3 and D4 dopamine receptors, the question arises as to which subtype performs what role(s). To investigate the potential autoreceptor roles of these proteins, D2, D3 and D4 receptors were transfected into a mesencephalic clonal cell line which synthesizes and releases dopamine. Here we report that stimulation of transfected D2 and D3 receptors, but not D4 receptors, inhibits dopamine release from this dopaminergic cell line. This is the first report of a functional role for D3 receptors and establishes these cell lines as a convenient in vitro model system to study signal transduction mechanisms associated with autoreceptor function.

Topics: 4-Aminopyridine; Animals; Cell Line; Dopamine; Ergolines; Humans; Membrane Potentials; Quinpirole; Rats; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Dopamine D4; Recombinant Proteins; Salicylamides; Tetraethylammonium; Tetraethylammonium Compounds

Fos expression in the globus pallidus (GP) of rats was elicited by the D2 agonist quinpirole both ipsilateral and contralateral to a unilateral nigrostriatal 6-hydroxydopamine (6-OHDA) injection; however, the 6-OHDA-treated hemisphere was more sensitive to this effect. The quinpirole-induced GP Fos expression was antagonized in both hemispheres by the D2 antagonist eticlopride, but not by the D1 antagonist SCH 23390. In neurologically intact rats, the D1 agonist SKF 38393, which alone did not elicit pallidal Fos expression, augmented the quinpirole-induced Fos response. Thus, D1 agonists can synergize with D2 agonists in inducing GP c-fos; but the D2-stimulated induction does not depend on concurrent D1 agonism.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Benzazepines; Corpus Striatum; Dopamine Agents; Dopamine D2 Receptor Antagonists; Ergolines; Functional Laterality; Gene Expression; Genes, fos; Globus Pallidus; Male; Oxidopamine; Proto-Oncogene Proteins c-fos; Quinpirole; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, Dopamine D2; Salicylamides; Substantia Nigra

The effect of administration of subtype selective dopamine (DA) agonists on the 6-hydroxydopamine (6-OHDA) lesion-induced increase of striatal preproenkephalin (PPE) mRNA was examined by dot-blot hybridization. Eight days following a unilateral 6-OHDA lesion of the substantia nigra pars compacta (SNc), PPE mRNA levels in the ipsilateral striatum were increased approximately two-fold. Administration of the D2 DA agonist, quinpirole, dose-dependently attenuated the 6-OHDA lesion-induced increase in striatal PPE mRNA. The effect of quinpirole was blocked by coadministration of the D2 DA antagonist eticlopride. In contrast, administration of the D1 DA agonist, SKF 38393, either dose-dependently augmented or had no effect on the 6-OHDA lesion-induced increase in striatal PPE mRNA. In the contralateral striatum, administration of quinpirole decreased PPE mRNA, while administration of SKF 38393 increased PPE mRNA compared to sham lesioned control levels. These data suggest the action of DA at D1 and D2 DA receptors differentially regulates striatal PPE mRNA levels and the apparent inhibition of ENK biosynthesis by DA is mediated via an interaction with D2 DA receptors.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Blotting, Northern; Corpus Striatum; Desipramine; Dopamine; Enkephalins; Ergolines; Gene Expression Regulation; Kinetics; Male; Nucleic Acid Hybridization; Oligonucleotide Probes; Oxidopamine; Protein Precursors; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Reference Values; RNA, Messenger; Salicylamides; Stereotaxic Techniques

Using electrophysiological techniques, we studied interactions of dopamine and selected dopaminergic drugs with serotonin (5-hydroxytryptamine; 5-HT) receptors expressed in Xenopus oocytes by RNAs transcribed from cloned cDNAs. Oocytes showing strong expression of 5-HT1c and 5-HT2 receptors became weakly responsive to the neurotransmitter dopamine, which, like 5-HT, elicited Cl- currents through activation of the phosphatidylinositol/Ca2+ messenger pathway. The two types of 5-HT receptors showed similar sensitivity to dopamine; threshold responses were activated at concentrations as low as 1 microM. However, maximum dopamine responses were only 5-20% of maximum responses activated by 5-HT. The dopamine D1 receptor antagonist SCH 23390 was a potent agonist on 5-HT1c and 5-HT2 receptors. SCH 23390 elicited currents at concentrations as low as 1 nM, but maximum responses were again only 5-20% of those activated by 5-HT. Fenoldopam, a dopamine D1 receptor agonist, also interacted with 5-HT1c and 5-HT2 receptors, eliciting threshold responses between 10 and 20 nM. Our experiments raise the possibility that low micromolar concentrations of dopamine can cause weak activation and concomitant desensitization of serotoninergic systems in vivo and demonstrate that benzazepines can interact with 5-HT receptors at nanomolar concentrations.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Benzazepines; Catecholamines; Cloning, Molecular; Dopamine; Dopamine Agents; Dose-Response Relationship, Drug; Ergolines; Female; Fenoldopam; In Vitro Techniques; Kinetics; Membrane Potentials; Oocytes; Quinpirole; Receptors, Serotonin; Salicylamides; Transcription, Genetic; Xenopus

The classical neurotransmitters serotonin and dopamine are thought to be involved in the etiology or treatment of a variety of psychiatric disorders. Recent studies suggest that these neurotransmitters may also have roles as neural morphogens during brain development. Previously, we have demonstrated that stimulation of serotonin 5-HT1A receptors selectively inhibited neurite branching in an in vitro system (Sikich et al 1990). In the present study, the developmental role of dopamine D2 receptors in the control of neurite outgrowth has been investigated by quantitating the morphological response of cortical neurons to agonist stimulation in vitro. Cultures of fetal rat frontal, cortical neurons were shown to express both alternatively spliced forms of D2 receptor messenger RNA (mRNA). The larger mRNA form predominated (D2A444:D2A415 ratio of about 6:1). In a small but significant percentage of these neurons, culture in the presence of the D2 receptor selective agonist, quinpirole, resulted in a three-to ten-fold increase in the length of neurites and in the number of branch points per neurite. These effects were blocked by the D2 receptor antagonists eticlopride and spiperone. Early abnormalities in the stimulation of dopamine or serotonin receptor subtypes could lead to the types of neuroanatomical changes observed in studies of schizophrenia, bipolar affective disorder, and autism. These morphogenic effects of classical transmitters could unite neurodevelopmental and neurotransmitter theories of the etiology of severe psychiatric disorders.

Topics: Animals; Base Sequence; Brain; Cells, Cultured; Cerebral Cortex; Ergolines; Female; Male; Mental Disorders; Models, Biological; Molecular Sequence Data; Nerve Growth Factors; Neurites; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Receptors, Serotonin; RNA, Messenger; Salicylamides; Spiperone

In an attempt to resolve experimental discrepancies regarding the mode of action of D2 receptor regulation following denervation or chronic receptor blockade, rats with extensive unilateral destruction of the mesotelencephalic dopaminergic projections induced by intracerebral 6-hydroxydopamine were injected daily for 21 days with either saline or the potent, selective D2 antagonist eticlopride (0.5 mg/kg, i.p.). Four days after the last injection of eticlopride or saline, rats were killed, and brain sections through the caudate-putamen and nucleus accumbens septi were incubated with [3H]spiroperidol or (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5- phenyl-1H-3-benzazepin-7-ol ([3H]SCH 23390) to assay D2 and D1 receptors, respectively. Autoradiographic analysis revealed that chronic eticlopride treatment increased the density of D2 sites in the intact hemisphere for all regions examined without further augmenting the already increased density of D2 receptors seen in the dopamine-denervated hemisphere. D2 receptor density was independent of functional sensitivity as evidenced by the fact that rats treated chronically with eticlopride rotated contralateral to the 6-hydroxydopamine lesion following systemic administration of the selective D2 agonist quinpirole during the neuroleptic wash-out period, despite the fact that D2 receptor binding was not significantly different in the left and right hemispheres of these subjects. D1 receptor density was not affected by eticlopride treatment but was significantly reduced reduced in the dopamine-denervated hemisphere. [3H]Mazindol labeling of high-affinity DA uptake sites indicated that the extent of dopamine denervation was greater than 97% in both saline- and eticlopride-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Apomorphine; Autoradiography; Corpus Striatum; Denervation; Dopamine; Dopamine Agents; Ergolines; Hydroxydopamines; Male; Mazindol; Nucleus Accumbens; Oxidopamine; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Receptors, Dopamine D2; Salicylamides; Tritium