PubMed Health⌕ Search

Biomedical subjects

A S Lippa

Publications and source records attributed to A S Lippa.

13 recordsLinked to original sources
PubMed1979

Resolution of two biochemically and pharmacologically distinct benzodiazepine receptors.

Brain-specific binding sites have been isolated on synaptosomal membrane fragments which recognize pharmacologically active benzodiazepines (BDZ's) and triazolopyridazines (TPZ's). While early evidence indicated the existence of a single homogeneous class of BDZ binding sites, more recent biological and pharmacological studies support the notion of BDZ receptor multiplicity. We now propose that two biochemically distinct BDZ receptors exist in brain which are responsible for the mediation of different pharmacological activities. Type I BDZ receptors display a high affinity for both BDZ's and TPZ's, are not coupled to GABA receptors or to chloride ionophores, and are the sites which mediate anxiolytic actions. Type II BDZ receptors display a high affinity for BDZ's, display a low affinity for TPZ's, are coupled to GABA receptors and/or chloride ionophores, and are the sites which mediate pharmacological effects other than anxiolytic activity.

Animals↗
PubMed1979

Endocrine factors contributing to the ethanol preferences of rodents.

Groups of C57 Bl/6j mice (alcohol preferring) and DBA/2j mice (alcohol avoiding) were fasted for 24 hours and administered glucose. At 30, 120 and 300 minutes after glucose, the C57 Bl/6j mice had significantly higher levels of plasma glucose than the DBA/2j strain. These differences were observed in comparable groups given either forced access or no access to alcohol. In ad lib fed animals never exposed to alcohol, C57 Bl/6j mice had higher levels of plasma insulin than DBA/2j mice. Plasma levels of glucose and corticosterone were not significantly different in ad lib or fasted animals. The injection of insulin zinc protamine to DBA/2j mice produced 100% convulsions within one hour, but produced to convulsions in C57 Bl/6j mice for as long as 4 hours after administration. These data demonstrate that an insulin resistancy exists in C57 Bl/6j mice which is not dependent upon any prior alcohol experience. Evidence supporting a functional relationship between this diabetogenic disturbance and alcohol preference was obtained in C57 Bl/6j mice which were allowed to choose between water or a 10% alcohol solution (v/v). Insulin zinc protamine produced a selective dose-dependent reduction in alcohol intake. Additional support is received from the discovery that Chinese hamsters, a species genetically predisposed to diabetes, display an impressive preference for 10% alcohol.

Alcohol Drinking↗
PubMed1979

A synthetic non-benzodiazepine ligand for benzodiazepine receptors: a probe for investigating neuronal substrates of anxiety.

CL 218,872 is the first non-benzodiazepine to selectively displace brain specific 3H-diazepam binding with a potency comparable to that of the benzodiazepines. Like the benzodiazepines, CL 218,872 increased punished responding in a conflict situation and protected against the convulsions induced by pentylenetetrazole. These three pharmacological properties are highly predictive of anxiolytic activity. Unlike the benzodiazepines, however, CL 218,872 was relatively inactive in tests designed to measure effects on neuronal systems which utilize GABA, glycine and serotonin as transmitters. Furthmore, CL 218,872 was relatively free of the ataxic and depressant side effects commonly associated with the benzodiazepines. Because of this high degree of selectivity, CL 218,872 may represent a new probe for investigating neuronal substrates of anxiety.

Animals↗
PubMed1979

Benzodiazepine receptors: cellular and behavioral characteristics.

Brain specific benzodiazepine receptors appear to mediate the pharmacological properties of benzodiazepines. A neuronal localization for these receptors is suggested by the parallel decrease in the number of benzodiazepine receptors and cerebellar Purkinje cells in "nervous" mutant mice. Electrophysiological results are compatible with an action of benzodiazepines on neuronally localized, physiological receptors. Biochemical, electrophysiological and behavioral experiments highlight the possible importance of frontal cortex in mediating the anxiolytic properties of the benzodiazepines. Triazolenetetrazoles act upon benzodiazepine receptors, increase punished responding and protect against penetylenetetrazole-induced convulsions, but do not produce the side effects associated with benzodiazepines or affect classical neurotransmitter systems. The structural similarities between triazolopyridazines, purines and the indole portion of certain peptides may provide insights into the nature of the endogenous ligand.

Animals↗
PubMed1978

Bimodal distributions of highest ethanol acceptance concentrations in two strains of rats.

Two groups of non-deprived male Wistar rats and one group of male Sprague-Dawley rats were offered a choice of water and daily-increasing concentrations of ethanol. Each group's distribution of highest ethanol acceptance concentrations approximated a bimodal distribution with respect to concentration. Further, rats in each group which drank ethanol at high concentrations maintained relatively constant intakes of pure ethanol. These results are discussed in terms of taste and olfaction, central nervous system sensitivity and emotionality.

Alcohol Drinking↗
PubMed1978

Enhancement of 3H-diazepam binding by SQ 65,396: a novel anti-anxiety agent.

SQ 65,396, a clinically active anti-anxiety agent, enhanced the binding of 3H-diazepam at 1.5 nM. This effect was due to an increase in the affinity for the ligand, without a change in the number of 3H-diazepam binding sites. This action of SQ 65,396 may mediate its anti-anxiety effects by affecting the action of an endogenous modulator of the "benzodiazepine receptor." Several other substances and treatments increase the affinity of 3H-diazepam for its receptors by mechanisms which may be related to the effect produced by SQ 65,396.

Animals↗
PubMed1978

Relationship between benzodiazepine receptors and experimental anxiety in rats.

The in vitro and in vivo ability of benzodiazepines to inhibit specific 3H-diazepam binding correlated with their ability to increase punished responding in a conflict situation. Conflict and foot shock, the punishing stimulus used in most conflict procedures, also altered 3H-diazepam binding. These data implicate 3H-diazepam binding sites in mediating at least some of the anxiolytic properties of benzodiazepines and suggest the existence of some endogenous substance which might be involved in the etiology of anxiety.

Animals↗
PubMed1978

The neuropharmacological actions of amoxapine.

Amoxapine possesses a broad spectrum of psychotropic actions, including antidepressant and neuroleptic effects in animals. Antidepressant activity is characterized by its ability to inhibit tetrabenazine-induced depression, antagonize reserpine-induced hypothermia and enhance yohimbine lethality. Neuroleptic activity is demonstrated by the ability of amoxapine to decrease locomotor activity, induce ptosis and catalepsy, inhibit apomorphine gnawing and amphetamine stereotyped behavior and by characteristic changes in monkey discriminated avoidance behavior. The fact that punished responding in squirrel monkeys was present was present after repeated administration may indicate an anti-anxiety action of this drug. Evidence is offered that the conversion of the tertiary terminal nitrogen to a secondary amine may alter the pharmacologica properties of dibenzoxazepines in a similar way to the for the phenothiazines.

Amoxapine↗
PubMed1977

Effects of clozapine, chlorpromazine and diazepam upon adjunctive and schedule controlled behaviors.

Two twelve-animal groups of rats were trained to press a lever for food reinforcement under either a fixed ratio 20 (FR 20) or a fixed interval 2 min (FI 2 min) schedule. During the FI 2 min schedule a measure of adjunctive behavior (i.e., drinking) was taken. Each group was then administered various doses of chlorpromazine (2.5, 5.0, 10.0 mg/kg, P.O.), clozapine (2.5, 5.0, 10.0 mg/kg, P.O.) or diazepam (5.0, 10.0, 15.0 mg/kg, P.O.) in a random order. All three drugs reliably reduced FR 20 response rates in a dose dependent manner, but chlorpromazine and clozapine were more potent in this regard. Chlorpromazine reduced FI 2 min responses rates especially in the terminal portions of the fixed intervals while diazepam generally elevated rates primarily in the min-portion of the interval. Clozapine produced a less defined effect on overall responding. All three drugs affected index of curvature. Only chlorpromazine was able to reliably reduce occurrence of adjunctive behavior and reinforcements.

Animals↗
PubMed1977

Use of DRL in differentiating anxiolytic and neuroleptic properties of CNS drugs.

Presented in this paper are the effects of chlorpromazine, clozapine, d-amphetamine and diazepam on DRL behavior in rats. D-Amphetamine and diazepam, which showed similar effects on response errors, could be identified on the basis of burst responding and drug interaction. Clozapine, a new antipsychotic agent which does not cause extrapyramidal side effect in man affected DRL behavior in the same way as did chlorpromazine. Thus, DRL schedules are probably not useful in differentiating various neuroleptic agents.

Animals↗