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Biomedical subjects

J B Malick

Publications and source records attributed to J B Malick.

At least 37 records · Page 2Linked to original sources
PubMed1980

Effects of isoproterenol and chlordiazepoxide on drinking and conflict behaviors in rats.

Isoproterenol, a beta-adrenergic agents, induced drinking in water-satiated rats. Isopropeternol exhibited significant anti-conflict activity on water-deprived rats in the Shock-induced Suppression of Drinking (SSD) procedure. Chlordiazepoxide (CDP), at the highest dose tested, also increased drinking in non-deprived naive rats. As expected, CDP demonstrated highly significant anti-conflict activity in thirsty rats (SSD test). These results suggest that in conflict procedures, where food or water is used as a reward, agents that affect the consumatory drive mechanisms could show up as "false positives." Moreover, agents that affect primary drives (e.g., CDP), in addition to their anti-anxiety activity, could show additive activity in such conflict procedures.

Animals↗
PubMed1979

The pharmacology of isolation-induced aggressive behavior in mice.

This review attempts to summarize the literature on the effects of drugs on isolation-induced aggression in mice. In spite of the fact that each investigator that was surveyed utilized different methodologies (e.g., induction techniques, testing conditions, scoring systems), the results from the various laboratories are generally in agreement in many respects. Fighting in isolated mice has been shown to be selectively antagnoized (i.e., antifighting activity at doses significantly below doses producing neurological impairment in isolated mice) by antidepressants, neuroleptics, anticholinergics, antiserotonergics, and antihistamines; however, aggression was nonselectively antagonized by anxiolytics, muscle relaxants, anticonvulsants, sedatives, and hypnotics. Emphasis is placed on the necessity to determine pharmacological selectivity whenever antagonistic effects are observed; this can only be accomplished by measuring neurological impairment (ataxia) in the isolated mice by utilizing a test such as an inclined-screen, preferably immediately following aggression testing. Since isolated mice have been shown to exhibit marked differences in drug sensitivities and in metabolic dispositions of many classes of drugs as compared to group-housed controls, statements concerning drug selectivity or specificity are meaningless without some evidence for a lack of neurological impairment in isolated, aggressive mice.

Aggression↗
PubMed1978

Selective antagonism of isolation-induced aggression in mice by diazepam following chronic administration.

Benzodiazepines are non-selective (i.e., they only inhibit aggression at doses producing concurrent neuromuscular impairment) antagonists of isolation-induced aggression in mice following acute administration. However, in the present study diazepam was shown to be a selective antagonist of fighting in isolated mice following chronic administration for 5 days. When administered chronically, selective tolerance rapidly developed to the general CNS depression produced by diazepam whereas the antifighting activity was not diminished and, in fact, tended to be enhanced following multiple drug administrations. Thus, the antagonism of fighting in isolated mice by diazepam does not appear to be due solely to general CNS depressant properties.

Aggression↗
PubMed1977

Quipazine-induced head-twitch in mice.

Quipazine has been reported to be a direct serotonin receptor agonist. In this laboratory, quipazine produced head-twitch in mice similar to that produced by the serotonin precursor, 5-hydroxytryptophan (5-HTP). Three antiserotonergic drugs (methiothepin, methysergide, and cinanserin) antagonized both the 5-HTP and quipazine-induced head-twitch responses. In addition, the quipazine response was significantly potentiated by a monoamine oxidase (MAO) inhibitor, pargyline. Since it is not likely that quipazine itself is metabolized by MAO, these results suggested that quipazine might cause release of endogenous serotonin. Parachlorophenylalanine, a serotonin depletor, significantly antagonized the potentiation of quipazine by the MAO inhibitor but failed to antagonize the head-twitch produced by quipazine itself. The present studies suggest that quipazine influences serotonin receptors in the brain to produce head-twitch by two mechanisms of action: (1) by direct serotonin receptor activation, and (2) indirectly by causing a release of endogenous serotonin.

5-Hydroxytryptophan↗
PubMed1977

Effect of substance P on medial forebrain bundle self-stimulation in rats following intracerebral administration.

The effect of Substance P infused intracerebrally via chronically implanted electrode-cannulae on self-stimulation induced from the same site was studied in rats. Substance P caused a significant depression of self-stimulation at 60 and 120 microgram/rat. Morphine infused into this site also caused significant depression of self-stimulation, but the doses were considerably lower than those of Substance P (5 and 10 microgram/rat). Pretreatment with naloxone, a narcotic antagonist, significantly antagonized the effects of Substance P on self-stimulation. It is proposed that Substance P modulates self-stimulation by the release of an endogenous morphine-like substance, but the possibility of a direct effect of Substance P was not ruled out.

Animals↗
PubMed1976

The role of serotonergic pathways in isolation-induced aggression in mice.

Male mice that became aggressive following four weeks of social isolation were treated with seven known serotonin receptor antagonists. All of the antiserotonergic drugs selectively antagonized the fighting behavior of the isolated mice; the antiaggressive activity was selective since, at antifighting doses, none of the drugs either significantly altered spontaneous motor activity or impaired inclined-screen performance. Antagonism of 5-HTP-induced head-twitch was used as an in vivo measure of antiserotonergic activity and a statistically significant correlation existed between potency as an antiserotonergic and potency as an antiaggressive. PCPA, a serotonin depletor, also significantly antagonized isolation-induced aggression for at least 24 hr postdrug administration. The interrelationship between cholinergic and serotonergic mechanisms in the mediation of isolation aggression was investigated. The involvement of serotonergic systems in isolation-induced aggression is discussed.

5-Hydroxytryptophan↗
PubMed1976

Antagonism of isolation-induced aggression in mice by thyrotropin-relasing hormone (TRH).

TRH was shown to be an extremely potent (ED50 = 0.04 mg/kg, IP) antagonist of isolation-induced aggression in male mice. The antifighting activity of TRH was selective in that it did not produce concurrent neurological impairment or significant alterations in spontaneous locomotor activity at antiaggressive doses. This activity of TRH appeared to be a direct affect on CNS structures since neither triiodothyronine nor any of the constituent amino acids of TRH antagonized aggression in isolated mice. The results are discussed in terms of the recent clinical effectiveness of TRH in some cases of mental illness (e.g., depression and schizophrenia).

Aggression↗
PubMed1976

Gamma-aminobutyric acid: selective inhibition of electrically induced head-turning following intracaudate administration.

GABA selectively antagonized head-turning elicited by electrical stimulation of the caudate nucleus in the rat when applied directly to the site of stimulation utilizing an electrode-cannula. Pretreatment with picrotoxin, a GABA antagonist, prevented the action of GABA on the head-turn response. This report provides in vivo evidence that GABA may play an inhibitory role in basal ganglia function. The findings are relevant to basal ganglia disorders in man.

Aminobutyrates↗
PubMed1975

Central versus peripheral anticholinergic activity as assessed by two in vivo procedures in mice.

The activity of tertiary and quaternary anticholinergic drugs was compared in two different test procedures designed to measure cholinolytic activity in mice. The four drugs utilized were atropine sulfate, atropine methylnitrate, scopolamine hydrobromide, and scopolamine methylnitrate. The results led to the conclusion that one of these test procedures, the induction of mydriasis (increase in pupil size), primarily measures peripheral anticholinergic activity whereas the other procedure, inhibition of physostigmine lethality, primarily measures anticholinergic activity in the CNS. These two test procedures can be utilized to characterize the nature of the cholinolytic properties of prospective therapeutic drug candidates.

Animals↗