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PubMed1992

Effect of raclopride on dopamine D2 receptor mRNA expression in rat brain.

Prolonged treatment with dopamine D2 receptor antagonists is known to elevate the density of dopamine D2 receptor binding sites in caudate-putamen and nucleus accumbens in rat and human brain. In this study we used the dopamine D2 receptor antagonist raclopride (3 mumol/kg, s.c.) to determine if a single injection or daily administration of this drug for up to 18 days changed the expression of dopamine D2 receptor mRNA in rat caudate-putamen and accumbens as measured by in situ hybridization. A single injection of raclopride did not significantly change the numerical density of dopamine D2 receptor mRNA-expressing neurons in any of the regions examined. A daily administration of raclopride for 18 days resulted in a 31% increase in the number of cells expressing detectable amounts of dopamine D2 receptor mRNA in dorsolateral caudate-putamen and in a 20% increase in the area of silver grains over individual hybridization-positive neurons in this brain region measured on emulsion-dipped slides. The region-specific increase in the D2 receptor mRNA level in dorsolateral caudate-putamen was confirmed by measurement of the hybridization signal on X-ray film autoradiograms. The levels of D2 receptor mRNA remained unchanged in medial caudate-putamen and accumbens after 18 days' treatment. The region-selective increase in dopamine D2 receptor mRNA expression in dorsolateral caudate-putamen indicates a differential regulation of dopamine D2 receptor mRNA expression in a subpopulation of caudate-putamen neurons by this neuroleptic. We suggest that the increase in dopamine D2 receptor density in caudate-putamen known to follow prolonged dopamine D2 receptor blockade to some extent is regulated at the level of gene expression.

Analysis of Variance↗
PubMed1992

Neuroleptics increase c-fos expression in the forebrain: contrasting effects of haloperidol and clozapine.

The mechanisms by which the atypical neuroleptic clozapine produces its therapeutic effects in the treatment of schizophrenia without causing the extrapyramidal side effects that are characteristic of most antipsychotic drugs remain unclear. Recently, a single injection of the typical antipsychotic haloperidol has been shown to increase c-fos expression in the striatum [Dragunow et al. (1990) Neuroscience 37, 287-294]. C-fos is a proto-oncogene that encodes a 55,000 mol. wt phosphoprotein, Fos, which is thought to assist in the regulation of "target genes" containing an AP-1 binding site. Because a wide variety of physiological and pharmacological stimuli increase c-fos expression, it has been proposed that Fos immunohistochemistry might be useful in mapping functional pathways in the central nervous system. The present experiments examined some potential neuroanatomical differences in the actions of clozapine and haloperidol by comparing their effects on c-fos expression in the medial prefrontal cortex, nucleus accumbens, striatum and lateral septum. The effects of the selective dopamine receptor antagonists SCH 23390 (D1) and raclopride (D2) were also examined. Haloperidol (0.5, 1 mg/kg) and raclopride (1, 2 mg/kg) produced large increases in the number of Fos-containing neurons in the striatum and nucleus accumbens. SCH 23390 (0.5, 1 mg/kg) reduced the number of Fos-positive neurons in the nucleus accumbens and striatum, and had no effect in the other regions. Neither haloperidol nor raclopride increased the number of Fos-positive neurons in the medial prefrontal cortex. Haloperidol, but not raclopride, produced a modest increase in c-fos expression in the lateral septal nucleus. Clozapine (10, 20 mg/kg) was without effect in the striatum; however, it significantly increased the number of Fos-positive neurons in the nucleus accumbens, medial prefrontal cortex and lateral septal nucleus. Destruction of mesotelencephalic dopaminergic neurons with 6-hydroxydopamine abolished the increase in Fos expression in the nucleus accumbens and striatum produced by haloperidol and raclopride, and also blocked the clozapine-induced increase in the nucleus accumbens. However, the inductive effects of clozapine and haloperidol on c-fos expression in the lateral septal nucleus and of clozapine in the medial prefrontal cortex were not affected by the 6-hydroxydopamine lesions. These results suggest that clozapine's unique therapeutic profile may be related to its failure to induce Fos in the striatum as well as its idiosyncratic actions in the lateral septum and medial prefrontal cortex. The effects of clozapine in these latter regions do not appear to be mediated by dopaminergic mechanisms.

Animals↗
PubMed1992

Subsets of neurotensin-immunoreactive neurons revealed following antagonism of the dopamine-mediated suppression of neurotensin immunoreactivity in the rat striatum.

The distribution of neurotensin-immunoreactive structures in the rat striatum was evaluated after blockade of dopamine neurotransmission by drugs that act presynaptically (6-hydroxydopamine, reserpine) and postsynaptically, preferentially at the D2 (eticlopride, haloperidol) and D1 [(R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepi n-7-ol, SCH-23390] receptor sites. Calbindin-D (mol. wt 28,000) immunoreactivity was used to delineate patch (striosome) and matrix in the caudate-putamen and core and shell in the nucleus accumbens. Antagonism at the D2 dopamine receptor and 6-hydroxydopamine lesions caused dense axonal immunoreactivity and moderate numbers of neurotensin-immunoreactive neurons to be distributed preferentially in the matrix of the caudate-putamen. D1 receptor antagonism was significantly less effective at eliciting neurotensin-immunoreactive neurons in the caudate-putamen. Reserpine or co-administration of the D1 and D2 receptor antagonists produced many neurotensin-immunoreactive neurons in both striatal compartments throughout the caudate-putamen and dense axonal neurotensin immunoreactivity in the medial patch compartment. To varying degrees, with SCH-23390 being least effective and reserpine most effective, all of the drug treatments elicited neurotensin immunoreactivity in neurons in the olfactory tubercle, rostral nucleus accumbens, accumbal shell and ventrolateral caudate-putamen, i.e. most of the ventral striatum.

Animals↗
PubMed1992

Intrastriatal dopamine-rich implants reverse the changes in dopamine D2 receptor densities caused by 6-hydroxydopamine lesion of the nigrostriatal pathway in rats: an autoradiographic study.

The aim of the present study was to test whether intrastriatal implants of embryonic dopaminergic neurons are able to normalize the lesion-induced hypersensitivity of striatal dopaminergic receptors. The ascending dopaminergic pathway of adult rats was unilaterally lesioned using 6-hydroxydopamine. Three weeks later a cell suspension obtained from the mesencephali of ED 14 rat embryos was implanted into the denervated striatum. Rotational responses to dopaminergic agonists were tested five months after implantation. One month later animals were killed and striatal dopaminergic receptor densities were quantified using autoradiography, the dopaminergic reinnervation of the host striatum being visualized with [3H]GBR 12935, a ligand labelling dopamine uptake sites. The lesion induced a behavioural hypersensitivity to dopaminergic agonists and lesioned animals displayed a strong rotation contralateral to the lesion in response to a test dose of the D1 agonist compound SKF 38393 (2.5 mg/kg) or of the D2 agonist LY 171555 (0.15 mg/kg). These responses were completely abolished by the graft. The normal distribution of D1 and D2 dopaminergic receptors in the rat striatum was similar to that described previously. Seven months after the lesion of the nigrostriatal dopaminergic pathway, the density of D1 receptors was not significantly affected while the density of D2 receptors was increased by about 25-50%. The implantation of embryonic dopaminergic neurons into the denervated striatum led to a slight decrease of D1 receptor densities and to a reversal of the lesion-induced increase of striatal dopaminergic D2 receptors six months later. Moreover, this reversal concerned not only the reinnervated striatal region but also extended into non-reinnervated areas of the striatum. It is concluded that grafts of embryonic dopaminergic neurons can normalize the density of dopaminergic D2 receptors.

Animals↗
PubMed1992

Dopaminergic drugs reverse the impairment of radial-arm maze performance caused by lesions involving the cholinergic medial pathway.

Pharmacological studies have shown that both cholinergic and dopaminergic transmitter systems are crucial for optimal choice accuracy in the radial-arm maze and that these systems interact in a complex fashion. Lesion studies have provided evidence that the basal nuclear complex of the forebrain, the origin of cholinergic projections to the cerebral mantle, may be critical for the cholinergic modulation of learning and memory. We have shown that knife-cut lesions of the medial cholinergic pathway significantly impair radial-arm maze choice accuracy performance. The current study examined the effectiveness of D1 and D2 ligands in counteracting this lesion-induced deficit. The adverse effects of medial cholinergic pathway lesions were diminished or reversed by daily treatment with a D1 agonist (SKF 38393), a D2 agonist (LY 171555) or a D1 antagonist (SCH 23390), but were not affected by treatment with a D2 antagonist (raclopride). The three beneficial treatments have previously been found to attenuate the adverse effects of nictonic or muscarinic blockade on choice accuracy performance in the radial-arm maze. The finding that these dopaminergic drugs ameliorate the memory deficit caused by lesions involving the cholinergic medial pathway suggests the importance of interactions between cholinergic and dopaminergic systems in radial-arm maze performance. These results may provide leads for the development of novel therapeutic approaches for treating human disorders thought to result from cholinergic hypofunction.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Subsets of neurotensin-immunoreactive neurons in the rat striatal complex following antagonism of the dopamine D2 receptor: an immunohistochemical double-labeling study using antibodies against Fos.

A study was done to determine if the Fos and neurotensin immunoreactivities elicited in the rat striatal complex by the selective dopamine D2 receptor antagonist, S(-)-eticlopride hydrochloride are co-localized in the same neurons. Following injections of eticlopride, Fos and neurotensin immunoreactivity were both non-uniformly distributed among the striatal compartments and subterritories. Fos was co-localized in a significant number of small, lightly neurotensin-immunoreactive neurons, but not in a larger subset of neurons with significantly greater median diameter that exhibited intense neurotensin immunoreactivity extending well into the dendritic arbor. It is proposed that neurotensin-immunoreactive neurons lacking Fos immunoreactivity are prominent following selective blockade of the dopamine D2 receptor and represent a subset of striatal neurotensin-immunoreactive neurons. Neurotensin-immunoreactive cells containing Fos nuclei represent a distinct subset, possibly the one that is dominant following administration of reserpine [Zahm (1992) Neuroscience 46, 335-350]. Insofar as Fos expression has been reported to accompany activation of striatonigral and striatopallidal neurons, the absence of Fos in the subset of neurotensin neurons displayed following D2 receptor blockade may be at odds with activation and perhaps is more consistent with inactivation and accompanying decreased release of neurotensin [see Frey et al. (1988) Neurochem. Int. 12, 33-38, and Bean et al. (1989) J. Neurosci. 9, 4430-4438] as a mechanism underlying the accumulation of neurotensin in that subset of striatal neurons.

Animals↗
PubMed1993

Dopaminergic modulation of pilocarpine-induced motor seizures in the rat: the role of hippocampal D2 receptors.

This study examined the role of hippocampal dopamine D2 receptors in the genesis of limbic seizures induced by muscarinic agonists in the rat. Pilocarpine, 600 mg/kg, elicited rapid and usually fatal convulsions. These were not affected by focal injections of saline (1 microliter) into both hippocampi. Pretreatment of the dorsal, but not the lateral hippocampus, with the D2 agonist trans-(+)-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-2H-pyrazolo-(3,4-g)quinol ine hydrochloride (LY 171555, 2 micrograms per side), did not alter the frequency of pilocarpine-induced convulsions, but significantly delayed their appearance and reduced their intensity. LY 171555 similarly increased the latency of seizures induced by focal hippocampal injection of carbachol (100 micrograms), without changing the frequency or the severity. The selective D2 antagonist raclopride, injected dorsally into both hippocampi dose-dependently facilitated motor seizures evoked by pilocarpine (100 mg/kg), the cholinomimetic at this dose being ineffective as a convulsant in saline-treated animals. Intrahippocampal administration of the D1 agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF 38393, 2 micrograms per side) did not facilitate pilocarpine seizures and did not potentiate the proconvulsant action of raclopride. These data demonstrate that activation of the dopaminergic system, via D2 receptors in the dorsal hippocampus, is capable of protecting the animal against limbic motor seizures arising from excessive muscarinic stimulation of the hippocampus. Since the blockade of D2 receptors in the hippocampus markedly lowered the seizure threshold to pilocarpine, this would suggest that the dopaminergic input to the hippocampus is normally tonically active and functions physiologically to prevent epileptogenesis.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Dopaminergic regulation of cortical acetylcholine release: effects of dopamine receptor agonists.

The regulation of the basal forebrain cholinergic system by D1 and D2 dopamine receptors was assessed in the rat using in vivo microdialysis of cortical acetylcholine. The D1 agonist CY 208-243 significantly increased cortical acetylcholine release; in contrast, the D2 agonists quinpirole and (+)-4-propyl-9-hydroxynaphthoxazine were without significant effects. Moreover, when administered in combination with CY 208-243, quinpirole failed to potentiate the D1 agonist-induced increases in cortical acetylcholine release. The non-selective dopamine receptor agonist apomorphine also increased cortical acetylcholine release, and this was completely blocked by the selective D1 receptor antagonist SCH 23390 and slightly, but not significantly attenuated by the D2 antagonist raclopride. The present results indicate that stimulation of D1 receptors activates cortically-projecting cholinergic neurons; however, a minor contribution of D2 receptors cannot be excluded.

Acetylcholine↗
PubMed1995

Dopamine and complex sensorimotor integration: further studies in a conditioned motor task in the rat.

Rats were trained to depress a lever and wait for the onset of a light stimulus, occurring after four equiprobable and variable intervals. At the stimulus onset, they had to release the lever within a reaction time limit for food reinforcement. This paradigm required time estimation of the various intervals and high attentional load for correct performance. Following activation of the dopaminergic transmission after systemic injection of d-amphetamine (0.6 and 0.8 mg/kg) or intrastriatal injection of dopamine (2.5 microgram/microliters), the rat's performance was impaired. Compared with control animals, the performance deficits were expressed as an increased number of premature lever releases before the conditional stimulus onset ("premature responses") and decreased reaction times. Indeed, the reaction times distribution was shifted to the left towards shortened reaction times. Although the number of premature responses was increased, the time estimation of the four different equiprobable intervals was not disturbed after stimulation of dopaminergic activity. A delay-dependent shortening of reaction times as a result of the conditional probability of the stimulus occurrence (i.e. reaction times are shorter as the duration of the delay increases) was found in control and drug sessions, indicating that the animals were still able to prepare their motor response (lever release) even after overstimulation of the dopaminergic transmission. In contrast, blocking dopamine receptors with the selective D2 antagonist raclopride was found to induce opposite effects on the reaction time performance. The number of delayed responses (i.e. occurring with a latency > 600 ms) was found to be significantly enhanced. Furthermore, the reaction times distribution showed a shift of the values to the right revealing a general tendency to lengthened reaction times. These results indicate that a "critical level" of dopamine activity (neither too low nor too high) in the striatum is necessary for a correct execution of the movement in a conditioned motor task with temporal constraint. Moreover, while delayed responses might reflect a motor impairment, anticipatory responses might reflect a "motor facilitation" revealed by a higher level of motor readiness, without disturbing time estimation nor attentional processes.

Animals↗
PubMed1994

Lateralized interdependence between limbicotemporal and ventrostriatal dopaminergic transmission.

The antipsychotic effects of dopaminergic antagonists suggest dopaminergic hyperactivity plays a role in schizophrenia. However, an elevated number of D2 dopamine receptors in the left putamen of non-treated schizophrenics has been reported which is consistent with a diminution of dopaminergic transmission in the ventral striatum. Morphological and functional studies have shown marked alterations in the left medial temporal lobe (entorhinal cortex, hippocampus, parahippocampus gyrus) of schizophrenics. As the entorhinal cortex and the ventral hippocampus project to the ventral striatum, the functional relationship between left temporal structures and the left ventral striatum may be impaired in schizophrenics. To assess the validity of this hypothesis, we investigated the existence of a preferentially left hemispheric interdependency between dopaminergic pathways in male rats. We found that dopaminergic projections in the entorhinal cortex and the ventral hippocampus regulate dopaminergic transmission in the nucleus accumbens, particularly in the left hemisphere. Temporal D2 dopamine receptors seem to be primarily involved in this effect. This lateralized interdependent functioning appears structurally based. These results may provide new insights into the pathophysiology of schizophrenic psychoses.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

The dopamine D2 antagonist remoxipride acts in vivo on a subpopulation of dopamine D2 receptors.

Dopamine D2 receptors were inactivated by N-ethoxycarbonyl-2-ethoxy-1,2,-dihydroxy-quinoline (EEDQ) (6 mg/kg i.p.). The reduction in dopamine receptors was monitored by quantitative receptor autoradiography using [125I]iodosulpiride or [3H]raclopride as radioligands. Pretreatment of male rats with haloperidol (0.3-3 mumol/kg i.p.) produced a dose-related, complete protection against the decrease in [125I]iodosulpiride binding induced by EEDQ in the dorsal and ventral striata and in all cortical areas examined. Raclopride (0.25-10 mumol/kg i.p.) produced the same pattern of effect as haloperidol but had a weaker effect. In contrast, remoxipride (1-40 mumol/kg i.p. or s.c.) only produced a partial protection against the dopamine D2 receptor inactivation by EEDQ. The results in the EEDQ test were related to the potency to block d-amphetamine-induced hyperlocomotion and the ability to induce bar-test catalepsy in the rat. The potencies in the behavioural tests were found to correspond to the in vivo occupancy for dopamine D2 receptors as evaluated by the EEDQ-induced decrease in D2 binding. However, remoxipride differed from both haloperidol and raclopride by showing a much reduced occupancy of dopamine D2 receptors at doses with behaviourally equipotent effects. The results support earlier suggestions that remoxipride in vivo may act on a subpopulation of dopamine D2 receptors.

Animals↗
PubMed1994

Temporal changes in the messenger RNA levels of cellular immediate early genes and neurotransmitter/receptor genes in the rat neostriatum and substantia nigra after acute treatment with eticlopride, a dopamine D2 receptor antagonist.

The cellular immediate early genes are involved in the transcriptional events associated with the dopaminergic regulation of neurotransmitter expression within neurons of the neostriatum. To characterize these events in detail, quantitative in situ hybridization histochemistry was used to assess the temporal effects of acute dopamine receptor blockade with eticlopride, a dopamine D2 receptor antagonist, on the messenger RNA expression of the immediate early genes and neurotransmitters/receptors in the caudate-putamen and ventral tegmental area/substantia nigra pars compacta of the rat. Groups of rats were injected with a single dose of either isotonic saline or eticlopride (0.5 mg/kg i.p.) and killed at various time intervals ranging from 5 min to 24 h and frozen brain sections processed by in situ hybridization histochemistry. Using computerized image analysis, the changes in messenger RNA expression for c-fos, c-jun, jun B, jun D, nerve growth factor I-A and nerve growth factor I-B and for neurotensin, glutamate decarboxylase, proenkephalin, the dopamine D1 receptor and the short and long isoforms of the D2 receptor were examined in the caudate-putamen. In the ventral tegmental area and substantia nigra pars compacta, the messenger RNA expression of the above early response genes and that for neurotensin, tyrosine hydroxylase, cholecystokinin and the D2 receptor isoforms were also examined. In the neostriatum, eticlopride caused a rapid increase in c-fos messenger RNA with significantly increased levels at 10 min (P < 0.01). The levels peaked at 30 min and thereafter declined to control levels. A similar profile was observed for jun B messenger RNA, although levels were still significantly (P < 0.01) elevated at 1 h and declined to basal levels thereafter. No significant changes were observed for c-jun, jun D, nerve growth factor I-A and nerve growth factor I-B messenger RNAs. In the dorsolateral neostriatum, there was an increase in proneurotensin messenger RNA 10 min after eticlopride, this increase becoming significant (P < 0.01) at 60 min. Levels were maximal at 2-6 h and decreased after 12 h to basal levels. There were small increases in proenkephalin messenger RNA, but these were not significant (P < 0.05) until 6 h after the injection. Eticlopride did not have any significant effects on the messenger RNA levels for glutamate decarboxylase, the D1 receptor and the short and long isoforms of the D2 receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

N-methyl-D-aspartate receptor blockade impairs behavioural performance of rats in a reaction time task: new evidence for glutamatergic-dopaminergic interactions in the striatum.

The effects of blocking glutamate transmission at the N-methyl-D-aspartate receptor subtype were studied in rats performing a conditioned reaction time motor task. Rats were trained to release a lever after the onset of a visual stimulus within a time limit to obtain food reward. The results showed that the performances of the groups receiving the N-methyl-D-aspartate receptor antagonists dizocilpine maleate (0.1 mg/kg) injected systemically or DL-2-amino-5-phosphonovaleric acid at the highest dose tested (5.0 micrograms/microliter/side) injected locally into the striatum changed significantly as compared to controls. The effects of these antagonists, consisting of an increase in the number of lever releases occurring before the visual stimulus onset ("anticipated responses"), were similar to those induced by injecting dopamine into the same striatal location. Both dizocilpine maleate and DL-2-amino-5-phosphonovaleric acid (5.0 micrograms/microliter) reversed the motor deficits, resulting in an increase in the number of lever releases after the time limit ("delayed responses") that were induced by the D2 dopamine receptor antagonist raclopride. Although these results partly confirm the existence of a functional antagonism between the glutamatergic and the dopaminergic systems in the striatum, opposite findings were obtained with the group that received intrastriatal DL-2-amino-5-phosphonovaleric acid at the lowest dose (0.5 micrograms/microliter/side). When given alone, 0.5 micrograms/microliter DL-2-amino-5-phosphonovaleric acid had no behavioural effects, but when jointly administered with dopamine or raclopride, it was found to reverse the effects of dopamine and to potentiate the motor deficits induced by raclopride. These opposite effects on the reaction time task observed after the intrastriatal injection of DL-2-amino-5-phosphonovaleric acid, depending on the dose tested, occurred only after a combined treatment with a dopaminergic agonist or antagonist and suggest that the level of the striatal dopaminergic activity may play a critical role in regulating the glutamate transmission via the N-methyl-D-aspartate receptors during the performance of complex sensorimotor tasks of this kind.

2-Amino-5-phosphonovalerate↗
PubMed1994

Antagonistic interaction between adenosine A2A receptors and dopamine D2 receptors in the ventral striopallidal system. Implications for the treatment of schizophrenia.

Recent studies have shown the existence of a specific antagonistic interaction between adenosine A2a receptors and dopamine D2 receptors in the brain. This A2a-D2 interaction seems to be essential for the behavioural effects of adenosine agonists and antagonists, like caffeine. In the present study quantitative receptor autoradiography and brain microdialysis were combined to demonstrate a powerful antagonistic A2a-D2 interaction in the ventral striopallidal system. In the presence of the A2a agonist (2-p-carboxyethyl)phenylamino-5'-N carboxamidoadenosine, dopamine exhibited a lower efficacy in displacing the radiolabelled D2 receptor antagonist [125I]iodosulpiride from the rat ventral striatum, specially in the nucleus accumbens. A tonic dopaminergic modulation of the striopallidal neurons from the ventral striopallidal system was demonstrated by a dual-probe approach, by infusing selective dopamine agonists and antagonists in the nucleus and by measuring dopamine extracellular levels in the nucleus accumbens and GABA extracellular levels in the nucleus accumbens and in the ipsilateral ventral pallidum. The infusion of (2-p-carboxyethyl)phenylamino-5'-N-carboxamidoadenosine in the nucleus accumbens induced the same postsynaptic changes as the D2 antagonist raclopride, i.e. an increase in pallidal GABA extracellular levels, without changing those levels in the nucleus accumbens. Furthermore, the coinfusion in the nucleus accumbens of low concentrations of (2-p-carboxyethyl) phenylamino-5'-N-carboxamido-adenosine and raclopride, which were ineffective when administered alone, induced a significant increase in pallidal gamma-aminobutyric acids extracellular levels. These results suggest that A2a agonists, alone or in combination with D2 antagonists, could be advantageous antischizophrenic drugs, as blockage of D2 receptors in the ventral striopallidal system appears to be associated with the antipsychotic activity of neuroleptics but not with their extrapyramidal motor-side effects.

Adenosine↗
PubMed1985

Photophobic and phototactic responses of Amoeba proteus in KCN and SHAM solutions.

The effects of the metabolic inhibitors KCN and SHAM on phototaxis and photophobic response in Amoeba proteus have been studied. Both drugs neither change amoebae photophobic response nor the phototactic reaction. The results indicate clearly that the negative phototactic orientation is not impaired by impediment of respiration thus it is not directly coupled to the differences in energy production in different parts of A. proteus body.

Amoeba↗
PubMed1993

Effect of dopamine agonists and antagonists on ethanol-reinforced behavior: the involvement of the nucleus accumbens.

Rats initiated to self-administer 10% ethanol (v/v) in an operant situation using the sucrose-substitution technique received bilateral n. accumbens or caudate nucleus microinjections of d-amphetamine (4, 10, and 20 micrograms/brain), quinpirole (4 micrograms/brain), and/or raclopride (0.1, 0.5, and 1.0 micrograms/brain). Only microinjections into the n. accumbens produced changes in rate and pattern of responding. With d-amphetamine, an increase in total responding and a slowing of initial response rate was seen, whereas with raclopride administration a dose-related decrease in total responding was observed with no alteration in momentary response rates. Drug-dependent behavioral rate and pattern differences suggest that DA activity in the n. accumbens influences ethanol reinforced behavior.

Analysis of Variance↗
PubMed1985

Decrease in hepatic microsomal UDP-glucuronosyl-transferase activity in rats and cattle with fascioliasis: impaired in vitro glucuronidation of oxyclozanide.

The effects of liver fluke infection (Fasciola hepatica) on hepatic microsomal UDP-glucuronosyl-transferase activity have been studied in microsomes from experimentally infected rats and naturally infected cattle to see if they explain the toxic episodes observed in parasite-infected animals subjected to intensive chemotherapy with the flukicidal drug oxyclozanide. Dramatic decreases in the activity of this enzyme system with the typical substrate p-nitrophenol were observed in both animal species, even when little or no degenerative lesions could be seen in the liver parenchyma. In vitro there was a similar loss of glucuronic acid conjugation of oxyclozanide by hepatic microsomes from infected cattle. In vivo this would result in slower elimination of the drug and in drug accumulation.

Animals↗
PubMed1990

Persistent effects of chronic exposure to styrene on the affinity of neostriatal dopamine D-2 receptors.

We have investigated whether chronic exposure to styrene could inflict persistent effects on the binding characteristics of dopamine D-2 agonist binding sites in rat neostriatal membranes. Styrene exposure (1000 ppm, 6 months, 16 h/d overnight, and left without exposure for another 5 months) caused a marked increase (+160%) in the IC50 value of dopamine without significantly affecting the total amount of specifically bound [3H]raclopride. The specific [3H]raclopride binding in membranes from subcortical limbic areas was too low to yield acceptable displacement curves. These data indicate that chronic exposure to styrene can induce a persistent decrease in affinity of the neostriatal dopamine D-2 agonist binding sites, possibly mediated by membrane perturbations.

Animals↗