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S M Antelman

Publications and source records attributed to S M Antelman.

At least 19 recordsLinked to original sources
PubMed1992

Amphetamine or haloperidol 2 weeks earlier antagonized the plasma corticosterone response to amphetamine; evidence for the stressful/foreign nature of drugs.

We inquired whether a single exposure to amphetamine (AM) or haloperidol (HALO) could modify the plasma corticosterone (CORT) response to a second injection of AM 2 weeks later. Male rats were injected with 4 mg/kg d-AM sulfate and tested for water intake for 5 h before sacrifice. Overall, AM induced water intake but none of the pretreatments altered this effect. By contrast, preexposure to AM, HALO or its vehicle 2 weeks earlier prevented the elevation of plasma CORT obtained when AM was administered without pretreatment. A combined pretreatment of HALO or its vehicle with AM produced an even greater blockade of AM-induced CORT elevation. Manipulations which prevented AM-induced drinking reduced the effectiveness of AM pretreatment in attenuating AM-induced elevation in CORT, suggesting that the pretreatment may have been sensitizing the effectiveness of a coping response--drinking--in reducing the CORT effect. Our findings also indicate that a dopamine agonist (AM), a dopamine antagonist (HALO) and a nonspecific stressor (acidic vehicle) can all induce the same, long-lasting action on CORT. This strongly suggests that the effects of AM and HALO in this instance cannot be explained in terms of their pharmacological actions, which are opposite to one another, but instead relate to their properties as stressful/foreign agents to the organism.

Amphetamine↗
PubMed1992

One brief exposure to a psychological stressor induces long-lasting, time-dependent sensitization of both the cataleptic and neurochemical responses to haloperidol.

Rats were exposed for 10 minutes to one of several enclosures graded in novelty. In one experiment they were then simply sacrificed and plasma corticosterone determinations made in order to obtain an index of the relative stressfulness of these enclosures. In a second experiment the animals received haloperidol and were tested for catalepsy, 2 hours or two weeks following the novel experience. The most novel experience, exposure to a black box, resulted in the highest corticosterone levels and was the only one of our pre-treatments to induce significant enhancement of catalepsy as well as alteration of nucleus accumbens dopamine levels, 2 weeks--but not 2 hours--later. These findings indicate that brief exposure of adult animals to a psychological stressor can induce a long-term alteration in both behavioral and neurochemical responses to a drug and that this effect requires a minimum level of stress to get started and once triggered gets stronger with the passage of time.

Animals↗
PubMed1991

One experience with 'lower' or 'higher' intensity stressors, respectively enhances or diminishes responsiveness to haloperidol weeks later: implications for understanding drug variability.

This laboratory has previously shown that acute exposure to a variety of brief stressful events can have a very long-lasting influence on subsequent responsiveness to pharmacological and non-pharmacological stressors. In some cases the response to these agents is enhanced, while in others it is diminished: the common denominator being that in each instance the influence of the initial stressor grows stronger with the passage of time. Here, we identify one factor that determines which time-dependent effect is manifest. In 3 separate experiments, male rats were subjected to a single exposure to stressors of either lower or higher intensity and their effects on haloperidol-induced catalepsy and dopamine and dihydroxyphenylacetic acid levels in the nucleus accumbens and medial frontal cortex, measured either 1-2 h or 2 weeks later. The stressors were either environmental (needle jab or 1 h of immobilization), metabolic (200 or 750 mg/kg, i.p. of 2-deoxy-D-glucose), or no effect on haloperidol-induced catalepsy when stressors preceded such behavioral testing by 1-2 h. By contrast, when the interval was 2 weeks, the lower-intensity stressors all increased haloperidol catalepsy, whereas the higher-intensity stressors decreased the same response. In other words, a process that progressed with the passage of time was observed regardless of whether sensitization or diminution of haloperidol's action occurred. In contrast to the uniform bipolar behavioral effects observed, depending on the intensity of the prestressor, the neurochemical findings failed to show any evidence of bipolarity whatever.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Conditioned tolerance to the anorectic and corticosterone-elevating effects of nicotine.

We have shown that tolerance to the behavioral effects of nicotine is partially dependent on conditioned environmental cues that predict drug delivery. The present research extends this finding to physiological effects of nicotine by assessing both the appetite-suppressing and adrenocortical-activating effects of nicotine, as measured by plasma corticosterone (CORT). In the first study, male rats on a 22-h food deprivation schedule were injected daily with 0.33 or 0.66 mg/kg (free base) of nicotine bitartrate or saline in a distinctive environment and tested for milk intake. Nicotine initially suppressed milk intake and tolerance developed over 10 days. Changing cues associated with drug administration partially reversed tolerance since injection of nicotine in a new environment reduced milk intake of tolerant animals. Similarly, animals who repeatedly received nicotine in one environment exhibited CORT levels lower than rats injected for the first time, and this tolerance also was partially reversed when administration occurred in the new environment. The second experiment indicated that the increased CORT of Experiment 1 was not a stress response associated with injecting animals in a different environment. These results indicate that tolerance to both behavioral and neuroendocrine effects of nicotine is influenced by conditioning.

Animals↗
PubMed1990

Immobilization 12 days (but not one hour) earlier enhanced 2-deoxy-D-glucose-induced immunosuppression: evidence for stressor-induced time-dependent sensitization of the immune system.

1. Prior exposure to a stressor can either increase or decrease subsequent behavioral, neurochemical, and endocrine reactivity to stress, depending on the pattern of stress exposure. 2. Massed or frequent exposures typically induce a reduction in reactivity whereas intermittent or widely spaced exposures increase subsequent reactivity. 3. In the present study, the authors examined whether a single presentation of a temporally remote stressor would increase the immunosuppressive effects of a subsequent stressor. Specifically, the authors investigated the effectiveness of 2-deoxy-D-glucose (2-DG) in suppressing the responsiveness of splenic lymphocytes in male, Sprague-Dawley rats that received either no prior treatment, or immobilization either one hour or 12 days earlier. 4. Splenic lymphocyte responsiveness to the T-cell mitogens, Concanavalin A (Con-A) and phytohemagglutinin (PHA) was suppressed following a single injection of 2-DG. 5. The group exposed to the stress of immobilization one hour prior to 2-DG demonstrated a comparable level of immune suppression. 6. In contrast, animals immobilized 12 days prior to the administration of 2-DG showed a more pronounced suppression of immune responsiveness which was significantly greater than the other groups injected with 2-DG. 7. Neither the stress-induced elevation in corticosterone, nor the suppression of blood lymphocyte reactivity to Con-A and PHA was enhanced by prior immobilization. 8. The results indicate that the immunosuppressive effects of an acute stressor can sensitize with the passage of time.

Animals↗
PubMed1989

Persistent sensitization of clonidine-induced hypokinesia following one exposure to a stressor: possible relevance to panic disorder and its treatment.

Based on previous findings of this laboratory that a single exposure to a stressful stimulus can induce a very long-lasting, sensitizing influence on the actions of drugs of multiple clinical and structural classes, the hypothesis was tested that a single stressful event might exert such an action on the alpha-2 norepinephrine agonist clonidine. Male rats received a single injection of the highly stressful convulsant stimulant pentylenetetrazole (PTZ; 40 mg/kg, IP) and were tested for locomotion after treatment with clonidine (25 micrograms/kg, IP) 1 h, 1 week or 2 weeks later. As expected, clonidine itself induced the hypokinesia typically associated with low doses of this compound. More importantly, all groups pretreated with PTZ showed a significant enhancement of this effect. The influence of PTZ 1 or 2 weeks prior to clonidine cannot be explained as simply due to a lingering impairment of locomotion by PTZ, since no hypokinesia was observed when activity in these groups was examined immediately prior to clonidine administration. Such impairment appears, however, to have been a factor in the heightened hypokinesia observed in the group receiving PTZ only 1 h before clonidine. Mass spectrometric analysis of norepinephrine and 3-methoxy-4-hydroxyphenylglycol levels in hippocampus and cortical areas failed to reveal any changes which could explain the persistent behavioral sensitization we observed. Plasma corticosterone determinations confirmed the stressful nature of PTZ but similarly failed to provide an explanation for the observed behavioral sensitization. The major finding of a long-term sensitizing influence on clonidine of an acute stressful experience is consistent with what is known of the precipitants and treatment of panic disorder.

Animals↗
PubMed1989

Prior stress attenuates the analgesic response but sensitizes the corticosterone and cortical dopamine responses to stress 10 days later.

This study demonstrates that pre-exposure to stress influences subsequent effects of stress on pain sensitivity (stress-induced analgesia) and on plasma corticosterone and brain catecholamine activity. Animals exposed to a 30 min shock session (S1 = 8, 5.0 s shocks) 10 days earlier showed a significant attenuation of shock-induced analgesia, as measured by increased latency of tail withdrawal from a hot water bath immediately after a 40 s, 1.6 mA footshock (S2). Animals exposed to shock 10 days before testing also exhibited a higher plasma corticosterone response to testing than did all other groups. Norepinephrine (NE) levels in the frontal cortex and dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels in the frontal cortex and nucleus accumbens were not altered in any group. However, the DOPAC/DA ratio in the frontal cortex was increased by analgesia testing, and this increase was enhanced only by the combination of shock 10 days before testing and shock immediately before the test (S1 + S2). These results are consistent with previous reports from this laboratory which indicate that an animal's acute response to stress is strongly influenced by its past history of stress.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

A single exposure to cocaine or immobilization stress provides extremely long-lasting, selective protection against sudden cardiac death from tetracaine.

Exposure of rats to one injection of cocaine (35 mg/kg, i.p.) or a single four-hour period of immobilization protected them from the virtually instantaneous death but not from the later, seizure-related death seen in untreated controls following administration of the local anesthetic, tetracaine, 1-4 weeks later. These data suggest that when appropriately timed, strong sympathomimetic stimulation--whether generated by an environmental stressor or a drug--can provide long-lasting protection against the sudden cardiac death potential of local anesthetics. As such, they provide a means for understanding why the incidence of sudden cardiac arrest from one such agent--cocaine itself--is not higher and suggest that an individual's stress history may play a key role in determining vulnerability to the cardiotoxic effect of this compound.

Animals↗
PubMed1989

Anticonvulsant and other effects of diazepam grow with time after a single treatment.

The hypothesis was tested that some of the effects in rats of the prototypical benzodiazepine, diazepam, would grow (i.e., sensitize) with the passage of time after acute administration as we had previously observed following stimulants, antidepressants, neuroleptics and other compounds. Our principal findings indicate that: 1) A single pretreatment with 0.5 mg/kg of diazepam significantly enhances the anticonvulsant effect of this same dose administered again two weeks later. 2) One injection of 2.5 mg/kg of diazepam significantly sensitizes the catalepsy and ptosis observed following the administration of haloperidol two weeks but not two hours later. These data provide the first evidence for time-dependent sensitization after benzodiazepines and perhaps by implication, of GABA neurons. They may also suggest that acute stimulation of GABA neurons triggers the progressive development of a long-term, antidopaminergic influence. Finally, they raise the question of whether the progressive anxiolytic influence seen during the first week or so of benzodiazepine therapy depends on the passage of time rather than repeated drug treatment.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

One stressful event blocks multiple actions of diazepam for up to at least a month.

Based on recent findings of this laboratory, the hypothesis was tested that a single stressful encounter might have a persistent antidiazepam influence. Our results indicate that one exposure to a brief stressful event up to at least one month earlier prevented completely the effect of diazepam on pentylenetetrazole-induced changes in dopamine in the rat frontal cortex, elevations of plasma corticosterone levels and seizures.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Behavioral effects of a single neuroleptic treatment grow with the passage of time.

The principal finding of this manuscript is that the incidence of catalepsy observed in the rat after a single administration of low, clinically relevant doses of the dopamine receptor antagonists and antipsychotic agents, haloperidol and fluphenazine hydrochloride, grows over time such that one re-exposure to the same compound up to 8 weeks later results in a marked enhancement (i.e. sensitization) of this response. This phenomenon appears to be independent of pharmacokinetic or conditioning factors as well as alterations in dopamine or dihydroxyphenylacetic acid. It suggests that the antidopaminergic influence of acute exposure to a neuroleptic not only persists but continues to sensitize for extraordinary periods of time even after the drug is no longer detectable in the system. Our findings may hold the key to understanding the apparent paradox that although neuroleptics presumably induce their therapeutic actions in disorders such as Tourette syndrome and schizophrenia as well as their parkinsonian effects by blocking dopamine receptors, this antagonism occurs immediately while behavioral changes often require weeks for maximal development.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Comparison of the effects of fenfluramine and other anorectic agents in different feeding and drinking paradigms in rats.

Fenfluramine (2.5 and 5 mg/kg) significantly suppressed the food intake of rats following food deprivation, administration of 2-deoxy-D-glucose (2DG), and during tail pressure. This suggests that fenfluramine has relatively general anorectic potency. Other "serotonergic" anorectics were studied for comparison. In a second experiment we determined that norfenfluramine and quipazine greatly suppressed food intake following food deprivation but, at the same doses, had relatively small effects on water intake following water deprivation. This was true for intraperitoneal and cerebroventricular routes of administration. The data have relevance for specificity of action of these agents and for the possible contribution of dopamine antagonist properties.

Animals↗