Biomedical subjects

D Wirtshafter

Publications and source records attributed to D Wirtshafter.

At least 37 records · Page 2Linked to original sources

PubMed1997

The distribution of reduced nicotinamide adenine dinucleotide phosphate-diaphorase in the leopard frog telencephalon and related projections.

The distribution of reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-D) was mapped histochemically in the forebrain of Rana pipiens, the leopard frog. Intense staining was observed which was strikingly restricted to certain nuclear groups and fiber tracts. The densest concentrations of NADPH-D stained cell bodies and fibers were observed in the granule layer of the accessory olfactory bulb and in the ventral aspect of the lateral pallium. Intense staining has also been reported in the presumed mammalian homologues of these regions. Less densely packed clusters of intensely stained neurons were found in the striatum, the anterior entopeduncular nucleus, the olfactory tubercle and the pars lateralis of the amygdala, whereas the preoptic region and the medial septum exhibited dense accumulations of lightly stained cells. Several fiber systems or terminal fields could be detected, including a ring of heavy staining which enclosed the striatum and an apparent terminal field in the lateral part of the medial pallium. A prominent compact tract, which may be homologous to a component of the stria terminalis of mammals, could be also followed from the ventral portion of the lateral pallium to the infundibular hypothalamus.

Animals↗

PubMed1996

Amphetamine induces Fos-like immunoreactivity in the striatum of primates.

Injections of D-amphetamine (5 mg/kg) three hours before sacrifice were found to elicit robust Fos-like immunoreactivity in the striatum of cynomolgus monkeys and of the common marmoset. Labeled cells were most frequently observed in the medial portion of the caudate nucleus and were distributed in a patchy fashion. Comparison with adjacent sections stained for the calcium binding protein calbindin indicated that the patches of amphetamine induced labeling corresponded to the calbindin-poor striosomes. These results are consistent with those reported in rats and thus suggest similarities in the basic organization of striatal mechanisms underlying the response to amphetamine in rodents and primates.

Amphetamine↗

PubMed1996

Fos-like immunoreactivity in the mamillary body and thalamus following injections of muscimol into the ventral tegmental nucleus of Gudden in the rat.

In many neurons, increased rates of firing are accompanied by expression of the proto-oncoprotein Fos. The current study examined Fos-like immunoreactivity in the mamillary body and the anterior thalamus following unilateral injections of the inhibitory GABA-A agonist muscimol into the ventral tegmental nucleus of Gudden (VTN). These injections resulted in a marked increase in Fos-like immunoreactivity ipsilaterally in both the medial mamillary nucleus and in its principle thalamic projection targets, the anteroventral and anteromedial thalamic nuclei. Since the projection from the VTN to the mamillary body has been shown to contain a substantial GABAergic component, these results are likely to reflect a disinhibition of mamillothalamic circuitry resulting from suppression of tonic inhibitory inputs arising in the VTN.

Animals↗

PubMed1995

Dopamine antagonists induce fos-like-immunoreactivity in the substantia nigra and entopeduncular nucleus of the rat.

Injections of the D2 receptor antagonists haloperidol (0.5-8 mg/kg) and metoclopramide (6.25-50 mg/kg) in rats resulted in a dose dependent induction of Fos-like-immunoreactivity in the rostral portion of the entopeduncular nucleus (EPN) and in the medial portion of the pars reticulata of the substantia nigra (SNpr). Nigral staining occurred exclusively in neurons which were not immunoreactive for tyrosine hydroxylase and could be antagonized by pretreatment with the anticholinergic drug scopolamine (3 mg/kg). Effects were much less pronounced following injections of the selective D1 antagonist SCH-23390 (2-8 mg/kg). No staining could be observed following administration of the 5HT3 antagonist MDL-72222 (10 mg/kg) or the 5HT1/5HT2 antagonist metergoline (5 mg/kg), suggesting that the effects observed with dopamine antagonists were not secondary to actions at serotonin receptors. These results are consistant with the hypothesis that blockade of dopamine receptors results in a disinhibition of cells within the SNpr and EPN and further suggest that examination of immediate-early gene expression may provide a useful tool for studying the extrastriatal circuit engaged by manipulations of dopaminergic transmission.

Animals↗

PubMed1995

Behavioral and neurochemical effects of opioids in the paramedian midbrain tegmentum including the median raphe nucleus and ventral tegmental area.

Injections of morphine into the median raphe nucleus (MR) of rats produced a dose-dependent, naloxone sensitive increase in locomotor activity. Dose-dependent increases in activity also could be produced by intra-MR injections of the mu-opioid agonist Tyr-D-Ala-Gly-MePhe-Gly(ol)-enkephalin (DAMGO) and the delta-opioid agonist D-Pen2,D-Pen5-enkephalin (DPDPE), but not by the kappa-opioid agonist Dynorphin A (1-13). Mapping studies demonstrated that DPDPE produced larger responses when injected into the MR than into a number of adjacent structures, whereas the effective zone for obtaining responses with DAMGO appeared to extend forward into the caudal portion of the ventral tegmental area. The induction of hyperactivity by DPDPE and DAMGO was unaltered in animals with large depletions of forebrain serotonin produced by injections of 5,7-dihydroxytryptamine, suggesting that these effects were not mediated through serotonergic mechanisms. Post-mortem assays indicated that serotonin turnover in the hippocampus was reduced slightly after intra-MR injections of DPDPE, but no effects were observed after injections of DAMGO or Dynorphin A (1-13). Injections of either DPDPE or DAMGO into the MR resulted in a large increase in dopamine turnover in the nucleus accumbens. Finally, intra-MR injections of DAMGO or Dynorphin A(1-13), but not DPDPE, stimulated ingestive behavior in nondeprived animals, although the effects were substantially smaller than those seen after injections of muscimol. These results demonstrate that pronounced behavioral and neurochemical effects can be produced by stimulation of opioid receptors within the MR and that the pattern of these effects depends upon which opioid receptor subtype is stimulated.

Animals↗

PubMed1994

Repeated D1 receptor agonist treatment blocks cocaine-induced locomotor activity and c-fos expression.

Pretreatment of rats for 4 days with the selective dopamine D1 receptor agonist A-77636 attenuated the ability of cocaine to induce locomotor hyperactivity and to stimulate the expression of the proto-oncogene c-fos in the striatum and nucleus accumbens. Our results suggest that repeated D1 agonist treatment leads to subsensitivity of D1 receptors involved in mediating some of the effects of cocaine on behavior and gene expression.

Adamantane↗

PubMed1994

Dopamine agonists and stress produce different patterns of Fos-like immunoreactivity in the lateral habenula.

In rats treated systemically with either amphetamine, amfonelic acid or apomorphine, large numbers of cells displaying Fos-like immunoreactivity (FLI) could be seen in the lateral zone of the lateral habenula. The induction of FLI by amphetamine could be blocked either by pretreatment with haloperidol or by 6-hydroxydopamine lesions of ascending dopamine fibers at the level of the lateral hypothalamus. In contrast, a variety of stressors selectively induced FLI in the most medial portion of the lateral habenula. These findings support the concept of a functional differentiation of the medial and lateral regions of the lateral habenula and provide further evidence for involvement of the habenula in the circuitry of the basal ganglia.

Animals↗

PubMed1994

Interactive effects of stimulation of D1 and D2 dopamine receptors on fos-like immunoreactivity in the normosensitive rat striatum.

Systemic administration of the selective, full, D1 dopamine agonist A-77636 [(1R,3S)3-(1'-adamantyl)-1-aminomethyl-3,4- dihydro-5,6-dihydroxy-1H-2-benzopyran hydrochloride] (0.36-2.9 mg/kg) led to a dose-dependent induction of Fos-like immunoreactivity (FLI) in the striatum. Quantitative analysis of the sections indicated that immunoreactive cells were more numerous in the medial than the lateral striatum and, within these regions, appeared to be randomly distributed. The staining produced by A-77636 could be abolished by pretreatment with the selective D1 antagonist SCH-23390. The selective D2 dopamine agonist quinpirole (3 mg/kg) had no effect on striatal FLI when given by itself, but markedly potentiated the weak striatal staining produced by low doses of A-77636. When combined with the highest dose of A-77636, which produced substantial staining by itself, quinpirole produced an increase in the number of immunoreactive cells seen in the lateral striatum but actually decreased the number present in the medial striatum. Statistical analysis of the distribution of immunoreactive cells demonstrated that, in both regions, quinpirole converted the relatively homogeneous staining seen after A-77636 alone into a markedly patchy pattern. These findings indicate that stimulation of D2 receptors produces both stimulatory and inhibitory effects on the D1-mediated expression of Fos in the striatum and that the interaction between D1 and D2 receptor stimulation must, therefore, be more complex than the simple synergism suggested by previous studies.

Adamantane↗

PubMed1993

Studies on the behavioral activation produced by stimulation of GABAB receptors in the median raphe nucleus.

Injections of the GABAB agonist baclofen into the median raphe nucleus (MR) resulted in marked hyperactivity and in increases in food and water intake by non-deprived animals. The locomotor effects of baclofen were stereospecific and could be antagonized by coinjection of the GABAB antagonist 2-hydroxysaclofen. Hyperactivity was produced by lower doses of baclofen, at shorter latencies, when the drug was injected into the MR than when it applied to the dorsal raphe nucleus (DR) or the ventral tegmental area (VTA). The locomotor response to intra-MR baclofen was unaltered in animals pretreated with the serotonin synthesis inhibitor p-chlorophenylalanine. Finally, intra-MR injections of baclofen produced a large increase in dopamine metabolism in the nucleus accumbens and striatum but failed to alter hippocampal or striatal serotonin metabolism. These findings suggest that baclofen may produce increases in activity and ingestive behavior as a result of an action on non-serotonergic cells in the MR.

Animals↗

PubMed1993

Evidence for GABAergic projections from the tegmental nuclei of Gudden to the mammillary body in the rat.

Immunochemical studies have demonstrated the presence of large numbers of cells immunoreactive for glutamic acid decarboxylase (GAD) within the dorsal and ventral tegmental nuclei of Gudden. Following injections of Fluoro-Gold into the medial mammillary nucleus, a substantial proportion of the retrogradely labeled neurons within the ventral tegmental nucleus displayed GAD-like immunoreactivity. Conversely, electrolytic or excitotoxic lesions of the ventral tegmental nucleus produced a large decrease in the number of fibers and terminals immunoreactive for GAD within the medial mammillary nucleus. In contrast, electrolytic lesions of the dorsal tegmental nucleus were found to produce a large decrease in GAD-like immunoreactivity which was restricted to the lateral mammillary nucleus. Control lesions placed caudal to the dorsal tegmental nucleus were without effect. These findings suggest that the dorsal and ventral nuclei send a substantial, topographically organized, GABAeregic input to the mammillary body.

Animals↗

PubMed1993

Effects of repeated dopamine D1 receptor stimulation on rotation and c-fos expression.

Acute injections of the full dopamine D1 receptor agonist A-77636 ((1R,3S)-3-(1'adamantyl)-1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1 H-2-benzopyran hydrochloride) induce ipsilateral Fos-like immunoreactivity and contralateral rotation into rats bearing unilateral dopamine depleting lesions. However, following repeated treatment, A-77636 fails to induce either striatal c-fos or rotation. Our results suggest that striatal c-fos activation mirrors behavioral indices of dopamine D1 receptor sensitivity.

Adamantane↗

PubMed1992

Nonserotonergic control of nucleus accumbens dopamine metabolism by the median raphe nucleus.

Injections of the GABA agonist muscimol into the median raphe nucleus (MR) have been shown to result in an acceleration of dopamine metabolism within the nucleus accumbens. To examine whether serotonergic mechanisms play a role in this effect, muscimol or its vehicle was injected into the MR of either control subjects or of rats that had received prior injections of the serotonin-depleting agent p-chlorophenylalanine (PCPA). Although PCPA treatments produced massive depletions of forebrain serotonin, they failed to alter the effect of muscimol infusions on dopamine metabolism. This finding suggests that the effects of intra-MR injections of muscimol on accumbens dopamine turnover do not result entirely from an interaction between serotonergic and dopaminergic systems.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Dissociation of haloperidol-induced "anhedonia" and catalepsy by lesions of the dorsal raphe nucleus.

Electrolytic lesions of the dorsal raphe nucleus were found to attenuate haloperidol-induced catalepsy, but did not alter haloperidol's ability to suppress the intake of a highly palatable saccharin/glucose mixture by nondeprived rats. These results suggest that neuroleptic-induced suppression of the drinking of palatable fluids is not secondary to the types of motor deficits that result in catalepsy.

Animals↗

PubMed1990

Ascending dopaminergic projections from the dorsal raphe nucleus in the rat.

The projections of putative dopamine containing cells within the dorsal raphe nucleus (DR) were studied using a combination of tyrosine hydroxylase (TH) immunocytochemistry and fluorescent retrograde tracing. Substantial numbers of TH-immunoreactive cells in the DR were found to project to the nucleus accumbens. Progressively smaller numbers of cells were found to project to the lateral septum and medial prefrontal cortex. Very few TH-immunoreactive cells projected to the dorsal striatum, and none to the substantia nigra. TH-immunoreactive cells did not display serotonin-like immunoreactivity. These findings indicate that the projection pattern of TH-immunoreactive cells within the dorsal raphe more closely resembles that of dopaminergic cells within the ventral tegmental area (VTA) than that of serotonergic cells within the DR.

Animals↗

PubMed1990

Control of food intake by kainate/quisqualate receptors in the median raphe nucleus.

In previous studies we have reported that increases in food and water intake can be produced by microinjections of both NMDA selective and broad spectrum excitatory amino acid antagonists into the median raphe nucleus (MR). In the current experiments we examined the influence of kainate/quisqualate receptors in the MR on ingestive behavior. The consumption of food and water by deprived rats could be suppressed by intra-MR microinjections of the excitatory amino acid agonists kainic acid (5-10 ng in 0.5 microliters vehicle) and quisqualic acid (125-500 ng). Conversely, intra-raphe injections of the kainate/quisqualate receptor antagonists pBB-PZDA (1.25-2.5 micrograms) and GAMS (10-20 micrograms) elicited feeding in nondeprived animals. pBB-PZDA was more potent in eliciting ingestive behavior than was the selective NMDA antagonist 2-amino-6-phosphonohexanoic acid, suggesting that the effects of pBB-PZDA were not mediated through the NMDA receptor. The current findings suggest that ingestive behaviors are tonically inhibited by excitatory amino acids acting at kainate/quisqualate receptors in the vicinity of the MR.

Animals↗

PubMed1990

Evidence for dopamine involvement in reinforcement obtained using a latent extinction paradigm.

The current experiment utilized a modified latent extinction method to examine the question of whether neuroleptic treatment blunts the reinforcing properties of food. Deprived rats were trained to traverse a runway for food reward and were then injected with haloperidol and given ten reinforced direct placements either into the goal box of the alley or into a novel cage with food present. The animals, while still under the influence of the haloperidol, were then given six standard trials of running down the alley. Animals who received goal box placements showed slower run speeds during the test trials than did the subjects who received placements into a neutral cage. These results suggest that placing the haloperidol treated rats into the baited goalbox resulted in a reduced expectation of reward and are compatible with the "anhedonia" theory of neuroleptic action.

Animals↗

PubMed1989

Behavioral and biochemical evidence for a functional role of excitatory amino acids in the median raphe nucleus.

Recent experiments have suggested the existence of excitatory amino acid (EAA)-containing afferents to the median raphe nucleus. In the present study we investigated the functional significance of EAAs in the median raphe (MR) by examining the behavioral and biochemical effects of intra-raphe injections of EAA antagonists. Injections of kynurenic acid, gamma-glutamylglycine, 2-amino-5-phosphonovaleric acid (2-APV) and 2-amino-7-phosphonoheptanoic acid (2-APH) into the median raphe resulted in marked hyperactivity. In contrast to the effect of 2-APV and 2-APH, intra-raphe injections of the homologues of these compounds with 4, 6 or 8 carbon atoms, which have a lower affinity for excitatory amino acid receptors, were without significant effects on activity. Additionally, the effects of 2-APV were shown to be stereospecific to the active D-isomer further suggesting receptor mediation of the effect. Injections of EAA antagonists into the dorsal raphe nucleus or the ventral tegmental area were much less effective in increasing activity than were injections into the MR, suggesting anatomical specificity of the effect. Injections of 2-APV into the median raphe were also shown to result in a reduction of serotonin metabolism within the hippocampus and an increase in dopamine metabolism within the nucleus accumbens and the magnitude of both of these effects was positively correlated with the behavioral responses to the injections. These findings suggest that cells within the median raphe may be subject to a tonic excitation exerted through EAA receptors.

2-Amino-5-phosphonovalerate↗

PubMed1989

Comparative studies of locomotor behavior following microinjections of muscimol into various sites in the paramedian tegmentum.

Microinjections of various doses of muscimol into the median raphe nucleus, the dorsal raphe nucleus or the caudal portion of the ventral tegmental area elicited dose-dependent increases in locomotor activity. In contrast, injections into the rostral portion of the ventral tegmental area or the midline pontine tegmentum caudal to the median raphe were ineffective. Lower doses of muscimol were required to produce hyperactivity after injections into the median raphe than after injections into any of the other sites. These findings suggest that the median raphe nucleus is the most sensitive site in the paramedian tegmentum for the elicitation of hyperactivity by muscimol.

Animals↗