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H P Alpern

Publications and source records attributed to H P Alpern.

At least 19 recordsLinked to original sources
PubMed1998

The medial amygdaloid nucleus modifies social behavior in male rats.

Electrical stimulation of the medial amygdaloid nucleus (AME) produces a behavioral state in male rats that resembles the postejaculatory interval, but electrical recording from cells in the AME shows that they become active earlier in sexual behavior, around the time that the male first appears to become aware of estrus in the female. In an attempt to resolve which feature of sexual behavior was mediated by the AME, we stimulated the structure bilaterally in freely behaving males using voltage levels too low to produce the postejaculatory interval. We found that electrical activation of this kind facilitated sexual behavior when it would not otherwise occur (i.e., in the presence of a nonestrous female). However, the stimuli suppressed sexual behavior when it would normally occur (i.e., in the presence of a nonestrous female). We discuss alternative interpretations of the results in the context of a general model for the central organization of sexual behavior in males.

Amygdala↗
PubMed1998

Depression after mild traumatic brain injury: a review of current research.

Research pertaining to the occurrence of depression and/or depression symptomatology after a Mild Traumatic Brain Injury (MTBI) was reviewed. We found that methodological differences such as the criteria used to assess MTBI and depression, time that elapsed since brain injury, and control group variations confounded comparisons across studies. Nevertheless, the studies are consistent with at least a 35% prevalence of, and left frontal damage with depression after MTBI, an overlap of symptoms of depression and Postconcussion Syndrome (PCS), and indicate that depression can continue for many years following the injury. Our conclusion is that MTBI is the triggering event for a set of pathophysiological changes and a concomitant depressive episode in a vulnerable subset of the population. Due to a paucity of research, it cannot be definitively concluded that the underlying substrates of depression seen after MTBI and clinical depression are the same. Implications for future investigations are discussed.

Antidepressive Agents↗
PubMed1989

Patterns of convulsive susceptibility in the long-sleep and short-sleep selected mouse lines.

It has been hypothesized that the Long-Sleep and Short-Sleep mouse lines were bidirectionally selected for high and low brain excitability, and further, that these differences are mediated by the benzodiazepine/gamma-aminobutyric acid (GABA) receptor-chloride channel complex. Hence, mice from both lines were administered seven convulsants (bicuculline, pentylenetetrazol, 3-carbomethoxy-beta-carboline, picrotoxin, caffeine, flurothyl and strychnine) and myoclonic and clonic seizure latencies recorded. Supporting the original hypothesis, the results show that the two lines were differentiated by all of the convulsants and that in response to the drugs, three distinct convulsive patterns were found. Nevertheless, a simple genetic model accounting for these results was not evident. To further clarify these susceptibility patterns, a convulsant representing each of these patterns (bicuculline, pentylenetetrazol or caffeine) was administered in conjunction with the anticonvulsant-barbiturate phenobarbital or the benzodiazepine antagonist Ro 15-1788. Irrespective of the convulsant given, phenobarbital attenuated both myoclonus and clonus subsequent to all convulsants, while Ro 15-1788 had a more discrete anticonvulsant profile.

Animals↗
PubMed1987

Differential convulsive susceptibility of high-activity and low-activity selected mice in response to GABA antagonists.

Lines of mice selectively-bred for High and Low-Activity in an open-field maze were tested for seizure susceptibility to three analeptics: flurothyl, pentylenetetrazol and bicuculline. The major finding was that two replicate High-Activity lines were more susceptible to myoclonic convulsions but less susceptible to clonic convulsions than their respective replicate Low-Activity lines. The major exception to this finding was that the High and Low-Activity lines did not differ for bicuculline-induced clonus although females tended to conform to the general pattern. These results are interesting because they demonstrate that diametrically opposite susceptibility to myoclonus and clonus is not an isolated phenomenon. Similar seizure susceptibility patterns and activity differences have also been reported for the Long-Sleep and Short-Sleep selectively-bred mouse lines. Further, since the progenitor population of the High-Activity and Low-Activity lines were developed from strains that were also part of the progenitor population of the Long-Sleep and Short-Sleep lines, it is hypothesized that some of the same alleles underwent selection in both selective-breeding programs.

Animals↗
PubMed1986

Sedative-hypnotic anomalies related to dose of pentobarbital in long-sleep and short-sleep selectively-bred mice.

Hypnotic effects following administration of three doses of pentobarbital were evaluated in mice selectively-bred for differential hypnotic sensitivity to ethanol. Although the ethanol-sensitive Long-Sleep (LS) line displays greater sedation to a wide variety of CNS depressants (alcohols, barbiturates, benzodiazepines, general anesthetics), when compared to the ethanol-insensitive Short-Sleep (SS) line, the response pattern to pentobarbital remains equivocal. Thus, to clarify the effect of pentobarbital, certain variables (dose, sex, circadian rhythmicity) believed to be important in the expression of sleep time were evaluated. For all doses examined "sex" and "time of day tested" impacted on sleep time. With these provisos, 40 mg/kg consistently induced shorter sleep time in SS mice. The 60 mg/kg dose either failed to distinguish these two lines, or induced greater sleep times in the SS mice. The 80 mg/kg dose tended to have the same effect as the 60 mg/kg dose, but to a greater degree. Overall, it appears that for each line the dose response curve for pentobarbital is sigmoidal, but that the slope of the curve for the middle range of doses is greater for the SS line. Since pentobarbital has a unique effect on these lines of mice that is dissimilar to those reported for other barbiturates, the implication is that an additional factor, that is unimportant for other barbiturates, is essential for pentobarbital-induced hypnosis. Factors that could be responsible for this effect include differential metabolism of Gabaergic receptor dynamics.

Animals↗
PubMed1986

GABAergic drugs can enhance or attenuate chlordiazepoxide-induced sleep time in a heterogeneous strain of mice.

Evidence supports the notion that differences between the Long-Sleep and Short-Sleep selectively-bred lines of mice are attributable to differences in brain excitability and that these differences are mediated by activity of the GABAergic system. The general applicability of this hypothesis to other populations of mice was tested by using an outbred strain of mice. Specifically, a heterogeneous strain of mice was administered several doses of the hypnotic chlordiazepoxide. Additionally, the indirect GABA agonist AOAA, and the GABA antagonists bicuculline, picrotoxin and pentylenetetrazol were administered to independent groups in conjunction with chlordiazepoxide. The results clearly demonstrate that chlordiazepoxide dose-dependently increased hypnosis, while AOAA enhanced, and the antagonists attenuated sleep time. These findings can be used to support the contention that GABA mediates the bidirectional response of Long-Sleep and Short-Sleep mice to CNS hypnotic-depressants; and, further, show that GABA mediation of sleep time in mice is a general phenomenon.

Acetates↗
PubMed1986

Thiopental, phenobarbital, and chlordiazepoxide induce the same differences in narcotic reaction as ethanol in long-sleep and short-sleep selectively-bred mice.

Hypnotic effects following administration of thiopental, phenobarbital or chlordiazepoxide were evaluated in mice selectively-bred for differential hypnotic sensitivity to ethanol. For every dose employed, except one which had no effect, all three agents induced greater sedation in the ethanol-sensitive Long-Sleep (LS) line than in the ethanol-insensitive Short-Sleep (SS) line. Such findings with regard to the LS and SS lines suggest that the differences in sedative response to ethanol, as well as some barbiturates and benzodiazepines, may be mediated, in part, by a common mechanism. The second experiment showed that age of the subjects can be an important variable influencing hypnotic-induced sleep time. For thiopental, significant line differences occurred only with 150 day old mice, whereas chlordiazepoxide produced differences in 50, 75, 100 and 150 day old mice.

Age Factors↗
PubMed1985

Coping and seizure susceptibility: control over shock protects against bicuculline-induced seizures.

Rats were either given 80 escapable shocks, yoked inescapable shocks, restraint or given no treatment. Two hours later all subjects received i.p. injection of bicuculline (4, 6 or 8 mg/kg) and were immediately tested for latency to initial myoclonic jerk and clonus. The latency to clonic convulsion was dramatically affected by prior shock treatment, and the direction of this change depended upon the escapability/inescapability of the shock. Subjects that were given escapable shock showed a delay of onset to seizure, while subjects inescapably shocked demonstrated a decreased latency to clonus in comparison to restrained and naive controls. It was also demonstrated that if the subjects were tested immediately following a stress experience, both the 80 escapable and inescapable shock condition protected against bicuculline-induced seizures in comparison to the control condition. Finally Experiment 2 confirmed a previous finding that less stress, i.e., 20 inescapable shocks, protects against seizures when the animals are challenged with bicuculline either immediately or 2 h later. Our suggestion is that control over stress may facilitate GABAergic transmission, and this may be the mechanism whereby coping protects against the behavioral and physiological disruption produced by exposure to a stressor.

Adaptation, Psychological↗
PubMed1985

Evidence that the selectively bred long- and short-sleep mouse lines display common narcotic reactions to many depressants.

This report challenges the notion that the long-sleep and short-sleep selectively bred mouse lines display unique narcotic reactions to alcohols. First, we found that the specific ethanol sensitivity hypothesis is not supported by the relevant literature. Second, we found that much of the ambiguity with respect to this hypothesis concerns just pentobarbital. Consequently, the major intent of this paper was to further explore what effect pentobarbital had on these two mouse lines. Additionally, we examined the effects of barbital and ethanol. Our results for each of these compounds clearly indicate that when these mouse lines can be differentiated by particular doses the long-sleep animals always displayed greater narcotic reactions. In this inquiry only one sex was employed, and testing was always initiated at the same time of day. It is our contention that many of the equivocal findings that have been reported concerning pentobarbital are due to combining data from both sexes, circadian rhythmicity, and similar procedural variables.

Alcoholism↗
PubMed1985

Reinterpretation of the literature indicates differential sensitivities of long-sleep and short-sleep mice are not specific to alcohol.

This paper reviews the findings and conclusions of the literature pertinent to the Long-Sleep and Short-Sleep selectively-bred lines of mice and challenges the widely-held notion that the selective breeding program was successful in separating alleles for specific sensitivities to just alcohol. Rather, it is argued that these lines of mice were selected for differing activity of a more general process. Recent evidence, as well as reevaluated previous evidence, indicates that Long-Sleep mice are more sensitive to the soporific effects of three major classes of CNS depressants (alcohols, barbiturates, and benzodiazepines), as well as many other anesthesia-inducing compounds (adenosine, chloral hydrate, trichloroethanol, paraldehyde, nitrous oxide, enflurane, and isoflurane). Further, much evidence also supports the conclusion that most of these hypnotic-depressants and anesthetics could exert their soporific influence by a potentiation of GABA activity. The other characteristic of interest in this regard is susceptibility to convulsions. Short-Sleep mice have significantly lower thresholds to both flurothyl-induced and bicuculline-induced convulsions, as well as being more likely to suffer from paroxysms during ethanol withdrawal.

Animals↗
PubMed1980

Paradoxical effects of d-amphetamine upon seizure susceptibility in 2 selectively bred lines of mice.

The ontogeny and substrates of amphetamine-induced changes in flurothyl-induced myoclonic and clonic seizure thresholds were investigated in 2 selectively bred lines of mice. The long-sleep mice exhibited dose-dependent increases in myoclonic and clonic susceptibility following amphetamine, irrespective of age. The noradrenergic agonist clonidine and the dopaminergic agonist apomorphine produced increases in susceptibility comparable to those seen with amphetamine. The short-sleep mice, however, exhibited a dichotomous myoclonic response to amphetamine that was age-dependent. Between 15 and 35 days of age amphetamine decreased seizure susceptibility whereas increases in susceptibility were noted at later ages. With the exception of 80 days, amphetamine did not affect clonic thresholds. In respect to myoclonus, clonidine persisted in producing effects similar to those seen in the long-sleep mice whereas apomorphine exhibited the same ontogenetic alteration in effect seen with amphetamine. These results confirm that the short-sleep mice might be a naturally occurring animal model of preadolescent hyperkinesis. Furthermore, the neuropharmacological tests demonstrate that the paradoxical response to amphetamine in the young short-sleep mice is mediated via a dopaminergic mechanism that must undergo dramatic change during ontogeny.

Age Factors↗
PubMed1979

Maturational changes related to dopamine in the effects of d-amphetamine, cocaine, nicotine, and strychnine on seizure susceptibility.

The effects of four neural excitants (damphetamine, cocaine, nicotine, and strychnine) on myoclonic and clonic seizure susceptibility were investigated in two age groups (30 and 120 days) of short-sleep mice. Amphetamine and cocaine decreased susceptibility to myoclonus in young mice and increased susceptibility in mature mice. These effects were attenuated by pretreatment with haloperidol, indicating mediation by a dopaminergic system. Amphetamine did not alter clonic susceptibility in either age group of mice, whereas cocaine affected clonic susceptibility and myoclonus. These effects were not attenuated by haloperidol, indicating mediation by systems other than dopamine. Nicotine decreased susceptibility to myoclonus and increased susceptibility to clonus, whereas strychnine increased susceptibility to both types of seizure. Haloperidol, however, failed to alter any of these effects. These results are consistent with our previous work which suggests that a dopaminergic mechanism in these mice undergoes marked developmental changes between 30 and 120 days of age.

Aging↗
PubMed1978

Differential neurohumoral modulation of myoclonic and clonic seizures.

Differential effects of neuropharmacological drugs upon susceptibility to flurothyl-induced myoclonic and clonic convulsions were assessed in two selectively bred lines of mice. Dopaminergic drugs (apomorphine and haloperidol) only affected myoclonus, whereas cholinergic (pilocarpine and scopolamine), gabaergic (AOAA and bicuculline), and serotonergic (PCPA) compounds principally influenced clonus. Noradrenergic drugs (clonidine, phentolamine and sotalol), however, altered the expression of both types of seizures. The apparent differential neurohumoral modulation of myoclonus and clonus is discussed in light of previous suggestions that these behaviors have separate neural substrates.

Aminooxyacetic Acid↗
PubMed1975

Methaqualone: tolerance and physical dependence in mice.

Tolerance and physical dependence was produced in C57Bl/6 male mice that had been exposed, for 36 days, to methaqualone in food pellets via an automated system. Tolerance was revealed in the reduction of sleep-times following intraperitoneal injection of methaqualone. Physical dependence was manifested as an alteration in neural sensitivity to flurothyl-induced convulsions.

Animals↗