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G K Weiss

Publications and source records attributed to G K Weiss.

At least 19 recordsLinked to original sources
PubMed1996

Chronic imipramine treatment induces downregulation of alpha-2 receptors in rat's locus coeruleus and A2 region of the tractus solitarius.

Imipramine is an effective antidepressant agent that blocks the reuptake of monoamines. In order to understand some of its basic mechanisms of action, we investigated the effects of chronic imipramine administration (10 mg/kg, i.p.; 21 days) on the alpha-2 receptor population of several brain sites. Alpha-2 receptor density was estimated by in vitro autoradiography using [3H]Idazoxan. The densitometric analysis revealed a decreased receptor density in the A2 region of the tractus solitarius (20%) and locus coeruleus (16%). No changes were observed in the amygdala, pyriform cortex, periacueductal gray and the bed nucleus of the stria terminalis. These results suggest that chronic imipramine treatment selectively modulates the alpha-2 receptor population localized in the brain stem norepinephrine-rich nuclei and not in the population present on limbic structures innervated by noradrenergic terminal projections. The possible physiological consequences of this selective modulation of alpha-2 receptors are discussed.

Adrenergic alpha-Antagonists↗
PubMed1994

The effect of two different types of stress on locus coeruleus alpha-2 receptor binding.

The central noradrenergic neurons of the locus coeruleus (LC) are important in regulating an animal's response to a stressor. Changes in alpha-2 autoreceptors on LC neurons during stress could alter the functional state of the LC. We investigated the changes in binding of LC alpha-2 receptors immediately following 1 h and 4 h of two stressors: novelty + cold and prone restraint. We measured the specific binding of the alpha-2 receptor antagonist [3H]idazoxan in the LC of rats using in vitro autoradiography. Specific binding was increased after 1 h of novelty + cold exposure but decreased after 4 h, and after both 1 and 4 h of prone restraint. The increase after 1 h of stress may be due to the ability of LC neurons to regulate their own activity because this would produce a dampening of the high LC activity produced by the stressor. However, extended time and/or intensity of a stressor may overwhelm this initial response and produce an agonist-induced decrease in receptor binding.

Adrenergic alpha-Antagonists↗
PubMed1993

Amygdala kindling rate is altered in rats with a deficit in the responsiveness of the hypothalamo-pituitary-adrenal axis.

Fisher and Lewis rats were amygdala kindled in the morning and in the evening. Fisher rats displayed a diurnal variation in the rate of kindling through stage 2 which did not exist in the Lewis rats. Lewis rats also take much longer to kindle through stage 2 and a subcutaneous corticosterone pellet accelerates this rate. These observations are consistent with the hypothesis that the hormones of the hypothalamo-pituitary-adrenal (HPA) axis, particularly the glucocorticoids, play a role in epileptogenesis.

Amygdala↗
PubMed1993

Decrease in locus coeruleus [3H]idazoxan binding site density in genetically epilepsy-prone (GEPR) rats.

Deficits in norepinephrine synthesis, transmitter level, turnover and reuptake have been reported in the brain of genetically epilepsy-prone (GEPR) rats. We investigated the hypothesis that these alterations may trigger a compensatory downregulation of locus coeruleus alpha 2-adrenergic receptors and an upregulation of postsynaptic alpha 2-adrenergic receptor density in forebrain regions of GEPR rat brain. alpha 2-adrenergic receptor density was measured in the locus coeruleus and 7 forebrain regions of control and GEPR rats by in vitro [3H]idazoxan autoradiography. Specific [3H]idazoxan binding site density was decreased significantly in the locus coeruleus of both GEPR-3 and GEPR-9 rats compared to controls. No significant differences in specific [3H]idazoxan binding were observed in the 7 forebrain regions of GEPR-9 rats compared to control. Reduced locus coeruleus alpha 2-adrenergic receptor density in GEPR rats may produce a net increase in locus coeruleus noradrenergic cell firing, an effect which could, in part, offset the impact of reduced noradrenergic influence in GEPR rat forebrain. Additionally, decreased norepinephrine levels in GEPR rat brain may be a long-term consequence of reduced alpha 2-adrenergic receptor-mediated inhibition of locus coeruleus firing activity.

Adrenergic alpha-Antagonists↗
PubMed1991

Effect of restraint stress on prolactin and corticosterone levels in streptozotocin-induced diabetic rats.

Changes in neuroendocrine function have been shown to occur in diabetic animals. The aim of the present study was to examine both the prolactin (PRL) and corticosterone (CORT) responses to a short period of restraint stress after the animals had been made diabetic for six weeks. The streptozotocin - induced diabetic rats had resting CORT levels which were significantly higher than the control animals. Acute restraint significantly increased CORT levels in both the control and diabetic rats. The CORT levels after stress were higher in the diabetic rats. However, the magnitude of the response (percent increase) was less in these animals. The resting PRL levels were not significantly different in the diabetic and control animals. The PRL levels significantly increased in both the control and diabetic rats when they were exposed to the restraint stress. The PRL levels after stress were significantly less in the diabetic rats, indicating a blunted PRL stress response. These results indicate that the diabetic state can affect an animals PRL and CORT response to a new acute stress.

Animals↗
PubMed1991

Evidence of immunosuppression in the genetically epilepsy-prone rat.

Immune system function was examined in the genetically epilepsy prone (GEPR-9) rat and non-epileptic Sprague-Dawley control rats. Significant decreases in direct and indirect plaque-forming cell responses were observed in GEPR-9 rats immunized with sheep erythrocytes. Serum levels of IgM were also decreased in non-immunized GEPR-9 rats, providing additional evidence of immunosuppression. However, total serum levels of IgG were three-fold greater in GEPR-9 rats compared to control. These results suggest that the nature of the immune system deficit in the GEPR-9 is complex and may involve an active T-cell population stimulating an overproduction of IgG leading to a diminished capacity to respond to new antigen challenges. This immunological defect may underlie the enhanced susceptibility of GEPR-9 rats to infectious agents. The specific cause of this immune dysfunction is not known. Possible etiological factors include a breakdown in the communication between cells within the immune system or an alteration of neuroendocrine modulation of immune responses.

Animals↗
PubMed1990

Antikindling effects of locus coeruleus stimulation: mediation by ascending noradrenergic projections.

Electrical stimulation of the noradrenergic locus coeruleus (LC) delays the generalization of partial seizures during amygdaloid kindling by increasing the time spent in the earliest stages of seizure development. To determine whether noradrenergic axons projecting to the midbrain and forebrain are involved in this antikindling effect, we examined the effects of lesions of the dorsal noradrenergic bundle, induced by intracerebral infusions of 6-hydroxydopamine (6-OHDA), on kindling and the antikindling action of stimulation of the LC. Stimulation of the LC during amygdaloid kindling increased the number of afterdischarges (ADs) spent in the early stages of partial seizure and decreased the number of ADs spent in later stages of generalized seizure, as has been described previously. LC-stimulated rats also displayed longer durations of AD during early stages of kindling. The antikindling effect of LC stimulation was blocked by lesions of the dorsal bundle, whereas the facilitatory effects of LC stimulation on generalization and on the duration of AD were unaffected by the lesions. These results suggest that the antikindling action of LC stimulation is mediated by the ascending projections of noradrenergic neurons, presumably through enhanced release of noradrenaline. On the other hand, the facilitatory effects of LC stimulation on the development of later stages of seizure and on the duration of AD appear to be independent of the ascending dorsal bundle.

Afferent Pathways↗
PubMed1990

Transient elevation of amygdala alpha 2 adrenergic receptor binding sites during the early stages of amygdala kindling.

Enhanced noradrenergic neurotransmission retards but does not prevent the development of kindling. We previously reported that locus coeruleus (LC) alpha 2 adrenergic receptor binding sites are transiently elevated during the early stages of kindling development. Since the firing activity of LC noradrenergic neurons is partially regulated via an alpha 2 receptor-mediated recurrent inhibition, the transient elevation in LC alpha 2 receptors could decrease LC activity and consequently facilitate the development of kindling. Transient elevation of alpha 2 receptor binding sites during early stages of kindling may also occur on noradrenergic axon terminals projecting to forebrain sites. Using in vitro neurotransmitter autoradiography techniques, we investigated this hypothesis by measuring specific [3H]idazoxan binding in 5 different areas of rat forebrain at 2 different stages of kindling development. After 2 class 1 kindled seizures, specific [3H]idazoxan binding was elevated significantly in the amygdala, but not in other forebrain regions. No differences in specific [3H]idazoxan binding were observed in any of the 5 brain regions in rats kindled to a single class 5 kindled motor seizure. Saturation of binding experiments indicated that the increase in amygdala [3H]idazoxan binding, following 2 class 1 kindled motor seizures, was due to an increase in the total number of alpha 2 receptor binding sites without a change in the affinity of the binding sites for [3H]idazoxan. Thus, the transient increase in alpha 2 receptors that occurs in the LC in the early stages of kindling also occurs in the forebrain region in which the kindled seizure originates.

Amygdala↗
PubMed1989

Transient elevation of locus coeruleus alpha 2-adrenergic receptor binding during the early stages of amygdala kindling.

Enhancement of noradrenergic neurotransmission retards, but does not prevent, the development of kindling. The firing activity of noradrenergic locus coeruleus (LC) neurons is partially regulated by axon collateral recurrent inhibition mediated via alpha 2-adrenergic receptors. We tested the hypothesis that LC autoinhibitory alpha 2-adrenergic receptors may change during the kindling process thereby altering LC excitability. Specific binding of the alpha 2-adrenergic receptor antagonist [3H]RX781094 (idazoxan) was measured in the LC of rats at 3 different stages of kindling development using in vitro neurotransmitter receptor autoradiography techniques. Specific [3H]RX781094 binding was elevated significantly in rats kindled to two Class 1 kindled motor seizures. No differences in binding were observed in animals kindled to Class 3 or Class 5 kindled motor seizures. Saturation of binding experiments indicated that the increase in binding following two Class 1 kindled motor seizures was due to an increase in the total number of alpha 2-receptors without a change in the affinity of the binding site for [3H]RX781094. The transient increase in number of LC alpha 2-adrenergic receptors is consistent with the idea that noradrenergic neurotransmission inhibits the early progress of kindling development, but then subsequently becomes ineffective in maintaining the inhibition during later stages of kindling development.

Amygdala↗
PubMed1989

The effect of amygdala kindled seizures on locus coeruleus activity.

Locus coeruleus (LC) neuronal activity was recorded in anesthetized and in awake behaving rats during the production of amygdala afterdischarges (AD's) using kindling protocol. Both LC multiple and single unit discharges were temporally correlated with the appearance of AD's in the amygdala. Seizures were manifested in single unit activity as significant increases in firing rate. In awake animals, a bursting pattern of discharges was observed. We postulate that the observed changes in the LC activity pattern may have a modulatory role in the development of kindled seizures.

Action Potentials↗
PubMed1987

Effect of locus ceruleus stimulation on the development of kindled seizures.

The effects of locus ceruleus stimulation on amygdala kindling development were investigated. Twenty to thirty minutes of locus ceruleus stimulation was delivered prior to each amygdala kindling session. Locus ceruleus-stimulated animals spent a significantly longer time in stage 1 than did nonstimulated or reticular formation stimulated controls. However, the total number of stimulations to produce the first stage 5 did not differ between groups. The afterdischarge duration in locus ceruleus-stimulated animals increased even though the behavioral stages did not progress. There appeared to be an uncoupling of the electrographic and behavioral manifestations of the kindling process in the locus ceruleus-stimulated animals. These data support the view of an inhibitory role of the central noradrenergic system in the development of kindled seizures.

Animals↗
PubMed1986

Avoidance behavior and plasma prolactin levels in lergotrile mesylate treated rats.

We have previously shown that psychological factors play a major role in control of prolactin (PRL) secretion, and that PRL increases during shock-motivated avoidance conditioning. In the present studies, we examined whether we could attenuate acquisition performance by suppressing the PRL increase during avoidance testing. Rats were tested daily in a shuttle box. They were presented with a light stimulation followed by an electric footshock. During each trial, the rats were given the opportunity to escape the footshock by moving to a safe side of the box. Movement to the appropriate location after the warning signal (light) begins, but before the onset of the footshock, constitutes a conditioned avoidance response (CAR). Experimental rats were fitted with an intraperitoneal osmotic minipump which delivered lergotrile mesylate (LM), 0.69 mg/kg/day. Blood samples were collected from an indwelling cannula and analyzed by radioimmunoassay. Administration of LM blocked the PRL increase that occurred during early avoidance testing, but did not alter the acquisition of a CAR. These data do not support the idea that PRL acts to facilitate acquisition of avoidance behavior.

Animals↗
PubMed1985

Plasma prolactin levels during conditioned avoidance behavior in rats.

In these experiments, we examined the prolactin (PRL) response during the acquisition of a conditioned avoidance response (CAR). Rats were tested daily in a two-way shuttle box. They were presented with a light stimulation followed by an electric footshock. During each trial period, the rats were given the opportunity to escape the footshock by moving to a safe side of the box. Movement to the appropriate location after the warning signal (light) begins, but before the onset of the footshock, constitutes a CAR. Blood samples were collected from an indwelling cannula and analyzed by radioimmunoassay. PRL levels increased during early acquisition testing, when the rats had not learned to avoid the shock. After one week of testing, acquisition performance increased considerably (70% CARs) while PRL levels remained unchanged. Thus, we were able to show that as rats learned to modify their behavior in response to a stressful situation, they could also modify their PRL response to the stressor.

Animals↗
PubMed1985

Habituation of the prolactin response in rats to psychological stress.

It is well known that stress is a stimulant for prolactin release. However, relatively few studies have investigated the role of psychological factors in prolactin secretion, and investigators have typically used one-time exposure and a single collection period in their studies. In our studies, attempts were made to carefully characterize the prolactin response to different psychological stressors by serially sampling blood from an indwelling cannula and to determine if repeated exposure to the stressor leads to habituation of the prolactin response. Exposure of the male rats to different novel situations such as being placed in a new cage, being placed on a platform in water, or being handled resulted in increased prolactin levels. As the rats habituated behaviorally to repeated exposure to similar situations, the prolactin response also attenuated. These findings show that psychological factors do play a role in influencing prolactin secretion and are consistent with the idea that as the psychological stress imposed by a stimulus becomes habituated, the prolactin response to that stimulus also becomes habituated.

Animals↗
PubMed1984

Effect of corticosterone on the prolactin response to psychological and physical stress in rats.

Both corticosterone and prolactin (PRL) levels increase in response to stress. In these studies we examined the effect of corticosterone on the PRL response to both physical (footshock) and psychological (novel environment) stress. Three groups of rats were used: sham adrenalectomized (SHAM), adrenalectomized (ADX), and adrenalectomized with corticosterone replacement (ADX+CORT). The corticosterone-treated animals received 80 micrograms corticosterone/ml drinking water. Blood samples were drawn via an indwelling cannula and PRL values determined using radioimmunoassay. ADX rats showed a consistently greater PRL response to being placed on a platform above water (novel environment) or when receiving intermittant footshock than did ADX+CORT rats. The PRL response of the latter group was similar to that of the SHAM animals. These findings indicate that corticosterone levels of an animal can significantly attenuate the magnitude of the PRL response to both physical and psychological stress. These findings further emphasize that the PRL response to stress is dependent not only upon the immediate action of the stressor, but also the prior stress history of the animal.

Adrenalectomy↗