Biomedical subjects

D Wirtshafter

Publications and source records attributed to D Wirtshafter.

At least 55 records · Page 3Linked to original sources

PubMed1989

Elicitation of feeding, drinking, and gnawing following microinjections of muscimol into the median raphe nucleus of rats.

Previous studies have demonstrated that injections of muscimol into the median raphe nucleus (MR) result in large increases in locomotor activity and food intake. The current experiment extends these results by showing that intra-MR muscimol injections in nondeprived rats also elicit nonprandial drinking and gnawing of wooden blocks. These findings indicate that stimulation of GABA receptors within the MR is able to energize a wide range of oral behaviors and is compatible with the view that the MR may be part of a "nonspecific" behavioral activation system.

Animals↗

PubMed1988

Comparative studies of the ingestive behaviors produced by microinjections of muscimol into the midbrain raphe nuclei of the ventral tegmental area of the rat.

Microinjection of the GABA-A agonist muscimol into the median (MR) or dorsal (DR) raphe nuclei or the ventral tegmental area (VTA) of non-deprived rats induced intense feeding and drinking in a dose-dependent and site-specific manner. Lower doses of muscimol were required to increase food intake, spillage and water intake with injections into the MR than with injections into the other two sites. These data demonstrate that the MR is a more sensitive site for the elicitation of ingestive behavior than either the DR or the VTA.

Animals↗

PubMed1988

Is dopamine involved in the hyperactivity produced by injections of muscimol into the median raphe nucleus?

Many studies have shown that experimental manipulations of the median raphe nucleus are able to produce profound effects on locomotor activity. Other data indicate that the raphe nuclei may exert an inhibitory influence over dopamine systems projecting to the forebrain. These results raise the possibility that the median raphe's influence over locomotion may be mediated through alterations in forebrain dopamine release. We examined this possibility in the current report by studying the role of dopamine in the hyperactivity produced by microinjections of the GABA agonist muscimol into the median raphe. Muscimol injections resulted in pronounced hyperactivity which was accompanied by a decrease in serotonin metabolism within the hippocampus and an increase in dopamine metabolism within the nucleus accumbens. Systemic injections of high doses of the dopamine antagonist haloperidol, however, were not able to attenuate muscimol's effect on activity. These results suggest that dopaminergic mechanisms do not play an essential role in mediating the effects of intraraphe muscimol on locomotor activity.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988

Stimulation of ingestive behaviors following injections of excitatory amino acid antagonists into the median raphe nucleus.

Anatomical and pharmacological evidence suggests that excitatory amino acids (EAA's) may function as neurotransmitters within the median raphe nucleus (MR). Previous studies have shown that injections of EAA antagonists into the MR result in marked hyperactivity. The current report extends these findings by demonstrating that intra-raphe injections of two EAA antagonists, kynurenic acid and 2-amino-5-phosphonovaleric acid, result in dose-dependent increases in food and water intake in nondeprived rats. These results suggest that EAA's within the MR may play a role in the control of appetitively motivated behaviors.

2-Amino-5-phosphonovalerate↗

PubMed1988

Evidence for a projection from the B9 serotonergic cell group to the median raphe nucleus.

Following injections of several fluorescent retrograde tracers into the median raphe nucleus large numbers of retrogradely labeled cells were observed in the ventral mesencephalic tegmentum. Subsequent immunocytochemical processing for serotonin-like immunoreactivity suggested that a large component of this projection originates from serotonergic B9 cells. Although tracer injections into the dorsal raphe did not result in similar labeling of B9 cells, evidence was obtained suggesting the existence of a small serotonergic projection from the median to the dorsal raphe.

Animals↗

PubMed1987

Evidence that serotonergic projections to the substantia nigra in the rat arise in the dorsal, but not the median, raphe nucleus.

Following microinjections of the fluorescent retrograde tracer Fast blue into the substantia nigra, large numbers of retrogradely labeled cells were observed in the dorsal raphe nucleus. Using immunocytochemical techniques it could be demonstrated that the majority of these cells contained serotonin-like-immunoreactivity. In contrast, careful examination of the region of the median raphe nucleus revealed no suggestion of a significant projection from the median raphe to the substantia nigra.

Animals↗

PubMed1987

Suppression of locomotor activity produced by acute injections of kainic acid into the median raphe nucleus.

Several lines of evidence suggest that cells within the immediate vicinity of the median raphe nucleus may exert an inhibitory influence on locomotor activity. If this theory were correct, one would expect that excitation of neurons within the median raphe would have a suppressive effect on behavior. This possibility was examined in the present study where low doses of the glutamate analogue kainic acid were injected into the median raphe nucleus of methylphenidate-pretreated rats. Our results indicate that these injections were able to antagonize, in a dose-dependent manner, both the horizontal locomotor activity and the nose poking induced by methylphenidate. These results provide further support for the existence of inhibitory median raphe influences on locomotion and suggest the possibility that endogenous excitatory amino acids may play a role in raphe functioning.

Animals↗

PubMed1987

Evidence against serotonin involvement in the hyperactivity produced by injections of muscimol into the median raphe nucleus.

Microinjections of muscimol into the median raphe nucleus were found to result in pronounced hyperactivity which could not be attenuated by the serotonin depletion produced either by systemic treatment with p-chlorophenylalanine or by intra-raphe injections of 5,7-dihydroxytryptamine. Furthermore, hyperactivity could not be produced by intra-median raphe injections of serotonin or of fenfluramine, compounds which would be expected to inhibit serotonergic raphe cells. These results argue strongly against an essential involvement of serotonin in mediating the effects of intra-median raphe muscimol injections. Muscimol failed to produce hyperactivity, however, when injected into rats who had previously received an electrolytic median raphe lesion. This finding suggests that muscimol injected into the median raphe produces hyperactivity as a result of an action on local cell bodies, rather than by diffusion to a distant site. The simplest explanation of the current results is that muscimol injected into the median raphe produces hyperactivity as a result of an inhibition of nonserotonergic cells within the median raphe nucleus.

5,7-Dihydroxytryptamine↗

PubMed1986

Serotonin-immunoreactive projections to the hippocampus from the interpeduncular nucleus in the rat.

The possibility of a serotonergic projection from the interpeduncular nucleus (IPN) to the hippocampus was examined using a combined immunohistochemical-fluorescence retrograde tracing technique. About one third of the cells in the apical subnucleus of the IPN which projected to the hippocampus could be shown to contain serotonin immunoreactivity, whereas double-labeled cells were only rarely encountered in the lateral subnuclei. These findings suggest that the IPN sends both serotonergic and non-serotonergic projections to the hippocampus and that the serotonergic projections arise primarily from the apical subnucleus.

Amidines↗

PubMed1986

Behavioral and biochemical studies of the substrates of median raphe lesion induced hyperactivity.

Many authors have demonstrated that electrolytic lesions of the median raphe nucleus lead to dramatic hyperactivity, but little is known as to the neural substrates of this effect. In the current series of experiments we investigated this question by examining locomotor activity and forebrain serotonin levels after the placement of wire knife cuts in various locations around the median raphe. Activity was measured in a five minute open field test and a one hour tilt cage test. Knife cuts designed to transect the major ascending serotonergic projections of the median raphe led to a pronounced depletion of forebrain serotonin, but had no effect on locomotor activity in either testing situation. Knife cuts located antero-ventral to the median raphe, designed to interrupt raphe connections with the ventral tegmental area and interpeduncular nucleus, increased activity in the tilt cage but not in the open field test. These cuts produced only small effects on forebrain serotonin levels. Knife cuts caudal to the median raphe failed to influence forebrain serotonin levels, but produced a significant increase in both open field and tilt cage activity. The effects of the posterior and the anteroventral cuts on tilt cage locomotion were additive, suggesting that different fiber systems were damaged by the two cuts. These results demonstrate that it is possible to double dissociate changes in forebrain serotonin levels and locomotor activity with lesions in the vicinity of the median raphe and further show that ascending projections are unlikely to be the only pathways involved in the effects of median raphe lesions on locomotor behavior.

Animals↗

PubMed1986

Discrimination learning and reversal following electrolytic lesions of the median raphe nucleus.

The current study examined the effects of electrolytic median raphe lesions on the performance of several T-maze discrimination tasks. Raphe lesions were found to impair the reversal, but not the acquisition, of a learned position habit, but to be without effect on either the acquisition or reversal of simultaneous brightness discrimination task. Rats with raphe damage were severely impaired in the acquisition of either a successive brightness discrimination task or of a delayed spatial alternation task. These results are similar to those which have been reported after limbic damage, and support the view that the paramedian midbrain tegmentum may play an important role in the functioning of limbic structures.

Animals↗

PubMed1985

Clonidine produces a conditioned place preference in rats.

The possibility that the alpha-adrenergic agonist clonidine can act as a reinforcing agent was investigated using the conditioned place preference paradigm. Using two different variants of this method we were able to demonstrate reinforcing properties of clonidine at doses of 200 and 400 micrograms/kg. These results are consistent with those obtained by other investigators using the self-administration technique, and support the view that adrenergic mechanisms may be involved in reinforcement.

Animals↗

PubMed1985

Pentobarbital-induced drinking does not rely on a renal dipsogen.

Injections of pentobarbital have been shown to produce drinking in both deprived and nondeprived rats and a number of other studies have shown that pentobarbital is a potent renin releasor. Since renin has been shown to be involved in thirst regulatory mechanisms and since the dipsogenic actions of other renin-releasing agents have been blocked by nephrectomy, we sought to determine whether or not pentobarbital-induced drinking relies on a renal dipsogen. Rats were either "sham" operated or nephrectomized under ether anesthesia. Five to six hours later, animals in each group were injected with either 9.5 mg/kg pentobarbital sodium or vehicle, and intakes were measured 60 minutes later. Statistical analysis of water intakes indicated that pentobarbital produced significant drinking in both control operated and in nephrectomized rats, and that the intakes in these two groups did not differ. These results indicate that pentobarbital-induced drinking is not secondary to increased plasma renin activity and may suggest the involvement of central mechanisms in the drinking response.

Animals↗

PubMed1985

Failure to establish a conditioned place preference with ethanol in rats.

Previous studies have demonstrated that many drugs of abuse are able to produce a conditioned place preference in rats. We sought to determine if ethanol, injected in a wide range of doses, could also produce a conditioned place preference. Statistical analysis of our results indicated that the IP administration of the drug (50, 100, 150, 300, 600, 800, or 1000 mg/kg) failed to produce either a conditioned place preference or aversion compared to vehicle injected control rats. Under similar testing conditions a conditioned place preference was obtained with amphetamine (2 mg/kg) and this preference was not secondary to conditioned hyperactivity. In another experiment, rats were injected with ethanol through indwelling jugular cannulae at doses similar to those reported [24,26] to support (1, 2 mg/kg) or not to support (8 mg/kg) self-administration by rats. We also failed to obtain a conditioned place preference using these doses. Blood and brain ethanol levels, determined 1, 2 or 5 minutes after the administration of 2 mg/kg (IV) indicated very low ethanol levels. These results may suggest that rats do not self-administer ethanol for its intoxicating properties, and that the affective state produced by ethanol administration per se is not readily conditionable to environmental cues.

Amphetamine↗

PubMed1985

Haloperidol and nonreinforcement produce different patterns of response slowing in a food reinforced runway task.

Rats were trained to traverse a runway for food reward and speeds were measured in the start, run and goal segments of the alley. After eight days of acquisition training, subjects were tested for four days under conditions of either extinction or haloperidol pretreatment. Although both haloperidol and extinction produced a suppression of the running response, the pattern of this suppression in the three alley segments was quite different for the two conditions. Haloperidol tended to be more effective than extinction in slowing start speeds but less effective than extinction in reducing run and goal speeds. This differential effect of haloperidol and extinction on speeds in different alley segments provides further evidence that haloperidol-induced impairments in performance cannot result entirely from a blunting of primary reinforcement.

Animals↗

PubMed1985

Electrolytic, but not 5,7-dihydroxytryptamine, lesions of the nucleus medianus raphe impair acquisition of a radial maze task.

We have previously reported that electrolytic lesions of the nucleus medianus raphe (MR) produce a deficit in the acquisition of an 8-arm radial maze task (Wirtshafter and Asin 1983). In an attempt to determine whether or not this deficit is secondary to serotonin depletion resulting from the lesion, we investigated and compared the effects of electrolytic and 5,7-dihydroxytryptamine (5,7-DHT) lesions of the MR on the acquisition of the radial maze task. Although forebrain serotonin levels after 5,7-DHT injections were reduced as much as those following electrolytic lesions, only rats with an electrolytic MR lesion were impaired on the acquisition of both a free-running maze task and on a related task, where animals were replaced into the same arm between arm choices. In contrast, 5,7-DHT-treated rats were unimpaired on both tasks compared to an ascorbate-injected control group. These findings provide further evidence that most of the profound behavioral deficits shown by rats with electrolytic MR damage are not due to serotonin depletion and are consistent with the results of other studies indicating strong similarities between the behavioral effects of limbic and MR lesions.

5,7-Dihydroxytryptamine↗

PubMed1983

Impaired radial maze performance in rats with electrolytic median raphe lesions.

Rats with electrolytic lesions of the median raphe nucleus were found to display a profound impairment in both the acquisition and retention of an eight-arm radial maze task. In contrast to neurologically intact animals, subjects with damage to the median raphe showed strong response patterning. When this patterning was disrupted by means of confinement, subjects with lesions responded at chance levels. As these results were similar to those which have been reported to follow hippocampal damage, this report provided further behavioral support for the concept of a functional relation between forebrain limbic structures and the midbrain tegmentum.

Animals↗

PubMed1982

Alterations in drug induced catalepsy and post-decapitation convulsions following brain and spinal cord depletion of norepinephrine by the neurotoxin DSP-4.

The effects of central norepinephrine depletion produced by DSP-4 on drug-induced catalepsy and pot-decapitation convulsions were examined in the rat. Haloperidol-induced catalepsy was potentiated in DSP-4 treated rats, while arecoline-induced catalepsy was attenuated. Furthermore, post-decapitation convulsions were eliminated in DSP-4 treated animals. DSP-4 may prove to be a useful tool with which to investigate the behavioral consequences of damage to the locus coeruleus noradrenergic system.

Amines↗