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E Yadin

Publications and source records attributed to E Yadin.

15 recordsLinked to original sources
PubMed1996

Effect of prenatal cocaine on dopamine receptor-G protein coupling in mesocortical regions of the rabbit brain.

The effects of in utero exposure to cocaine on dopamine receptors in the frontal and cingulate areas of the developing rabbit cortex were assessed by examining receptor-mediated stimulations in GTP binding to alpha-subunits of G proteins. Pregnant Dutch-belted rabbits received intravenous injections of 4 mg/kg of cocaine HCl twice a day on gestational days 8-29, cortical membranes were prepared from their progenies on postnatal days 10-100 and dopamine-stimulated [35S] guanosine-5'-[gamma-thio]triphosphate (GTP gamma S) binding to membrane G alpha proteins was measured. Dopamine increased [35S]GTP gamma S binding to G alpha s and G alpha i. These increases in [35S]GTP gamma S binding reflect the stimulation of D1- and D2-dopamine receptors, respectively. The ability of dopamine to stimulate the binding of [35S]GTP gamma S to G alpha s but not to G alpha i was reduced in both frontal and cingulate cortices obtained from cocaine-exposed animals when examined at 10, 50 or 100 days of age. Prenatal cocaine exposure was also shown to reduce dopamine-stimulated [alpha-32P]GTP binding to G alpha s without influencing binding to G alpha i. The muscarinic cholinergic receptor-evoked increases in [35S]GTP gamma S binding to G alpha i and G alpha o were not altered. Immunoblot analyses revealed no differences in the levels of these alpha subunits in membranes from cocaine-exposed animals vs controls. Furthermore, prenatal cocaine did not affect [3H]8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7- olhemimaleate binding to cortical D1 dopamine receptors. The results suggest that prenatal exposure of rabbits to cocaine selectively uncouples the D1 dopamine receptor from its G protein in mesocortical brain areas and that this change persists through postnatal day 100.

Animals↗
PubMed1995

Prenatal exposure to cocaine selectively reduces D1 dopamine receptor-mediated activation of striatal Gs proteins.

The effect of in utero exposure to cocaine on striatal dopamine receptors was assessed at postnatal days 10 through 100 by examining receptor-mediated increases in GTP binding to G alpha proteins. Pregnant Dutch-belted rabbits were injected with 4 mg/kg i.v. of cocaine HCl twice a day on gestational days 8 through 29, and striatal membranes were prepared from their progenies on days 10 through 100. Dopamine-stimulated [35S]GTP gamma S binding to membrane alpha subunits was measured and found to increase binding to G alpha s and G alpha i. Pharmacological characterization of the dopamine response revealed that enhanced [35S]GTP gamma S binding to G alpha s is associated with D1 receptor stimulation, whereas binding to G alpha i is linked to D2 receptor activation. The abilities of dopamine to stimulate the binding of [35S]GTP gamma S to G alpha s but not to G alpha i was reduced in striata obtained from cocaine-exposed animals when examined at 10, 50 or 100 days of age. Similarly, prenatal cocaine exposure also reduced dopamine-stimulated [alpha-32P]GTP binding to G alpha s without influencing binding to G alpha i. Fetal cocaine exposure did not change carbachol-induced increases in [35S]GTP gamma S binding to G alpha i and G alpha o. Immunoblot analyses showed no changes in the amounts of these alpha subunits in membranes from cocaine-exposed animals vs. controls. Moreover, prenatal cocaine did not affect [3H]SCH23390 binding to D1 dopamine receptors in the caudate, putamen or substantia nigra.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Anticonflict action of chlordiazepoxide in rats with combined lesions.

Lesions of brain areas thought to promote anxiety do not diminish the anticonflict effects of benzodiazepines (BZDs). After initial training in the lick-suppression conflict test, eight rats received electrolytic lesions of the amygdala, dorsal raphe, locus coeruleus, and mammillary bodies. Ten others received sham lesions. Postoperative testing revealed a significant increase in punished licking at two stages after surgery in lesioned animals when compared with their own preoperative baseline levels and with the punished licking of control animals. Systemic administration of chlordiazepoxide (CDP, 2.5-10.0 mg/kg) resulted in a comparable dose-dependent increase in punished licking in both groups. These results suggest that the several structures lesioned need not be intact for CDP to have an antianxiety effect. It appears that sites of anxiolytic action are much more widely spread than currently believed and that other brain areas should be considered.

Amygdala↗
PubMed1993

The role of the lateral septum in anxiolysis.

Behavior of rats in the water-lick conflict test was examined during stimulation, and after lesions of the lateral septal nucleus. Continuous low-current stimulation resulted in an anxiolytic effect, an increase in the number of licks, and hence in the number of shocks, during a signaled, punished period. This effect is similar to the one seen with peripheral administration of benzodiazepine and other anxiolytic agents. Rewarding medial forebrain stimulation did not have this effect. Conversely, septal lesions resulted in an anxiogenic effect, a significant decrease in the number of licks during the punished period. Lesions had this effect when the conflict behavior was already well established. Septal lesions performed before acquisition of the conflict behavior resulted in initial retardation of acquisition. The results suggest an important role for the lateral septum in the inhibition of anxiety and in the acquisition of behaviors reinforced by alleviation of anxiety.

Animals↗
PubMed1991

Septal unit activity during classical conditioning: a regional comparison.

Single unit activity was recorded from the lateral and medial septum of rats during aversive Pavlovian differential conditioning. One conditioned stimulus (CS+) was consistently paired with and another (CS-) was explicitly unpaired with a brief shock unconditioned stimulus (US). In the lateral septum single unit activity generally increased in the presence of a conditioned inhibitor of fear (CS-), while unit activity generally decreased in the presence of a conditioned excitor of fear (CS+). Responses in the medial septum were more heterogeneous. Many cells did not show plastic changes to the CSs, others showed responses to the conditioned stimuli opposite to that seen in the lateral septum. A small group of cells showed responses similar to that seen in the lateral septum. Finally, theta bursting cells were seen in the medial septum with some evidence of increased theta activity in the presence of a conditioned inhibitor of fear (CS-). The results were interpreted as consistent with the proposition that the lateral septum mediates the inhibition of aversive emotional states. The medial septum may have some involvement with the activation of fear or anxiety.

Action Potentials↗
PubMed1991

Anxiolytic effects of benzodiazepines in amygdala-lesioned rats.

The role of the amygdala in the anxiolytic action of benzodiazepines was examined. Performance on a water-licking conflict paradigm was tested in rats with localized damage to the central nucleus of the amygdala (ACE) or with general damage to the entire amygdaloid complex. The effects of the benzodiazepine chlordiazepoxide (2.5-20.0 mg/kg) on conflict behavior in these animals was also examined. Electrolytic lesions of either ACE or of the entire amygdaloid complex resulted in a pronounced increase of punished responding, an effect that persisted for at least 12 sessions postoperatively. After shock levels were adjusted in the lesioned groups to match their baseline punished behavior to that of the controls, various doses of chlordiazepoxide were administered. Not only did the lesioned animals show an increase in punished behavior in response to the drug, they were more sensitive than controls to the lower drug doses. A complete model of anxiolytic action may have to include both mechanisms that block anxiogenic regions and those that activate anxiolytic regions.

Amygdala↗
PubMed1991

Spontaneous alternation behavior: an animal model for obsessive-compulsive disorder?

This study entailed the adoption of a well-established behavioral paradigm, spontaneous alternation, as a possible animal model for some of the symptoms observed in obsessive-compulsive disorder (OCD) in humans. Food-deprived rats were run in a T-maze in which both a black and a white goal box were equally baited with a small amount of chocolate milk. Each rat was given 7 trials every other day during which it was placed in the start box and allowed to make a choice. The mean number of choices until an alternation occurred was recorded. After a stable baseline of spontaneous alternation was achieved the effects of manipulating the serotonergic system were tested. Both the nonselective 5-HT agonist 5-MeODMT (1.25 mg/kg) and the more selective 5-HT1A agonist 8-OH-DPAT (2 mg/kg) disrupted spontaneous alternation. A course of chronic treatment (2 x 5 mg/kg for 21 days) with the selective 5-HT uptake blocking agent fluoxetine had a protective effect on the 5-MeODMT-induced disruption of spontaneous alternation behavior. Serotonergic manipulations of spontaneous alternation may be a simple animal model for the perseverative symptoms or indecisiveness seen in people diagnosed with OCD.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Unit activity in the medial septum during differential appetitive conditioning.

Unit activity in the medial septal area of the rat was studied during pavlovian appetitive differential conditioning. The firing pattern of cells in the medial septum is that of suppression to presentation of the conditioned excitor and no significant increase to the presentation of the conditioned inhibitor. This pattern is discussed in the context of a comparison with the pattern found in the lateral septal area and assesses the significance of the motivational value of the stimuli.

Animals↗
PubMed1985

Forebrain origins and terminations of the medial forebrain bundle metabolically activated by rewarding stimulation or by reward-blocking doses of pimozide.

Using [14C]-2-deoxyglucose autoradiography, we determined which forebrain and diencephalic areas showed metabolic alterations in response to unilateral electrical stimulation of the posterior medial forebrain bundle at parameters chosen to produce a just-submaximal rewarding effect. At these parameters, only a few areas were activated. There was no detectable activation anterior or dorsal to the genu of the corpus callosum. Just anterior to the anterior commissure, there was strong activation of the vertical limb of the diagonal band of Broca, with a focus in the nucleus of the diagonal band. Just posterior to the anterior commissure, there was strong activation of compartment "c" of the medial forebrain bundle (MFB), with weaker activation of the bed nucleus of the stria terminalis and the medial preoptic area. At midhypothalamic levels, the dorsolateral, dorsomedial, and ventral MFB all showed activation. There was bilateral suppression of activity in the lateral habenula. Activation appeared to end in the anterior ventral tegmental area of Tsai. Reward-blocking doses of the neuroleptic pimozide activated the caudate and the lateral habenula but did not alter any of the unilateral effects of stimulation. Using longer pulse durations and/or shifting the site of stimulation to the substantia nigra activated many of the systems not activated in the first experiment, including all of the major dopaminergic projection systems, proving the capacity of the technique to reveal activation of these systems. The results permit one to define a discrete projection system that merits electrophysiological investigation as a likely substrate for the rewarding effect of MFB stimulation. They also suggest that dopaminergic projection systems may not form part of the reward pathway itself.

Animals↗
PubMed1983

Unilaterally activated systems in rats self-stimulating at sites in the medial forebrain bundle, medial prefrontal cortex, or locus coeruleus.

Rats with electrodes in either the posterior medial forebrain bundle (MFB), the anterior MFB, the medial prefrontal cortex, or the locus coeruleus self-stimulated during a 45 min period following the injection of [14C]2-deoxyglucose. They were then sacrificed and their brains prepared for autoradiography. The autoradiographs were analyzed for unilaterally activated neural systems, using a computerized image analyzing system to compare the darkness of neural structures on the stimulated side with the darkness of the same structures on the unstimulated side. There was extensive overlap in the neural structures unilaterally activated by stimulation in the anterior and posterior MFB; but there was no overlap between the structures activated by MFB stimulation and the structures activated by stimulation at either of the extradiencephalic sites; nor did the forebrain, diencephalic, and midbrain sites have any readily apparent bilateral effects in common. If there is a substrate common to MFB self-stimulation and extradiencephalic self-stimulation, its activation is not revealed by 2-deoxyglucose autoradiography.

Animals↗
PubMed1983

An animal model to detect learning deficits following treatment of the immature brain. Studies using radiation and methotrexate.

Learning deficits have been noted in children with acute leukemia given methotrexate (MTX) with and without cranial irradiation (RT) for prophylaxis. A rat model has been developed to assess treatment effects on learning. The test used was altered performance of a simultaneous discrimination task in a standard operant conditioning box, employing the mean number of days needed to score 80% correct responses as the criterion. An illustrative experiment distributed suckling rats among four groups: (1) 36 controls; (2) 14 cranial RT (1,000 R); (3) 14 MTX (5 mg/kg i.p.); (4) 36 RT + MTX 24 h later, and (5) 12 undernourished controls (to match poor weight gain patterns of treated animals). Survivors were tested 10-12 weeks later: values for groups 1-5 in order were 3.9, 4.1, 4.7, 5.0 and 4.0 days. Only group 4 results were significantly different from group 1 (p = less than 0.05).

Age Factors↗
PubMed1982

Computer assisted analysis of 2-DG autoradiographs.

A computerized image processing system is described that assists the neurobiologists in analyzing data from 2-DG autoradiography by providing for: (1) Rapid fine-scale digitization of gray levels using a TV camera (2) The recognition of and verification of subtle differences in optical density with the aid of color windows (3) the superimposition of the autoradiographic image upon the histological image, so that the activity seen in the autoradiograph can be accurately assigned to anatomically defined structures (4) The production of numerical data suitable for statistical analysis and line drawings suitable for black on white publication (5) The relating of local gray level to a norm for the image as a whole, so as to remove the variability introduced by variations in section thickness, in the amount of 2-DG seen by the brain during incorporation, in level of anesthesia, etc. If the localized darkening in autoradiographic images is being used as an index of localized functional activity rather than as a measure of metabolism, normalization obviates the need to obtain arterial blood samples. These routines permit anatomically accurate numerical analysis of autoradiographs without any constraints on the experimental situation.

Amygdala↗
PubMed1981

Septal correlates of conditioned inhibition and excitation in rats.

Multiple-unit activity was recorded in the lateral septum of rats during Pavlovian differential conditioning. In Experiment 1, one group of animals received a classical aversive discrimination paradigm, while another group was presented with a control procedure in which the unconditioned stimuli (shocks) were administered randomly with regard to the conditioned stimuli. Septal unit activity increased during presentations of the conditioned inhibitor and was markedly suppressed during presentations of the conditioned excitor in the conditioning-group animals and not in the control animals. Baseline activity remained unchanged in the conditioning group but was suppressed in the random control group. Furthermore, termination of the aversive stimuli was marked by a burst of firing in the conditioning group, but no such rebound was seen in the control group. In Experiment 2, a classical appetitive discrimination paradigm was given, in which septal unit activity was found to increase in the presence of the conditioned excitor and was suppressed in the presence of the conditioned inhibitor. The results are interpreted as indicating a role for the septum in the relief of aversive states.

Animals↗
PubMedDate not supplied

Stimulation of the lateral septum attenuates immobilization-induced stress ulcers.

Rats with electrodes implanted in their dorsolateral septal area underwent a cold-immobilization restraint procedure during which the experimental group received electrical stimulation while the control group did not. Electrical stimulation of the dorsolateral septal region clearly reduced the number of gastric ulcers formed during the cold-immobilization stress procedure. The pattern of results with septal stimulation contrasts with that seen by other investigators after stimulation of the central amygdaloid nucleus. The mitigation of stress-induced ulceration after lateral septal stimulation is consistent with the proposed function for the lateral septal area in relief from aversive emotional states.

Animals↗