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A M Allan

Publications and source records attributed to A M Allan.

44 records · Page 3Linked to original sources

Functional coupling of gamma-aminobutyric acid receptors to chloride channels in brain membranes.

gamma-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in mammalian brain, is believed to act by increasing membrane conductance of chloride ions. In this study it was found that GABA agonists increased the uptake of chloride-36 by cell-free membrane preparations from mouse brain. This influx was rapid (less than 5 seconds), and 13 micromolar GABA produced a half-maximal effect. The GABA antagonists (bicuculline and picrotoxin) blocked the effect of GABA, whereas pentobarbital enhanced the action. This may be the first demonstration of functional coupling among GABA and barbiturate receptors and chloride channels in isolated membranes. The technique should facilitate biochemical and pharmacological studies of GABA receptor-effector coupling.

Animals↗

Ethanol-induced grooming in mice selectively bred for differential sensitivity to ethanol.

In rats, excessive grooming follows the application of several forms of stress. The injection of alcohol may be considered as a stressor, since it increases plasma corticosterone levels. The present study examines the effects of ethanol injections on grooming in two lines of mice selected for differences in their hypnotic response to ethanol, i.e., the long sleep (LS) and short sleep (SS) lines developed at the Institute for Behavior Genetics at the University of Colorado at Boulder. Various subhypnotic doses of ethanol produced excessive grooming in the SS line, but this did not occur in the LS line. The SS mice also displayed more "novelty-induced" grooming compared to the LS mice after repeated exposure to the testing situation. The increase in excessive grooming in both the ethanol-induced and the novelty-induced excessive grooming situations was most apparent in the second half of the observation period.

Animals↗

Adrenergic nervous system alteration and ethanol-induced narcosis in long-sleep and short-sleep mice.

Long-sleep (LS) and short-sleep (SS) mice were pretreated with either propranolol or phentolamine, followed by a hypnotic dose of ethanol. Pretreatment with propranolol, but not phentolamine, significantly reduced ethanol sleep time in LS mice. The SS mice were not affected. In a second study propranolol pretreatment was given subsequent to ethanol at various doses, different for each line, that produced similar sleep time durations in both lines. Under these conditions, propranolol decreased sleep time in both LS and SS mice. These data lend support to the idea that noradrenergic mechanisms play a role in the mediation of the hypnotic effects of ethanol.

Adrenergic Fibers↗

Augmentation of latent inhibition by electrical stimulation of hippocampus.

The effects of low-level hippocampal stimulation on the development of latent inhibition were investigated employing classical conditioning of the nictitating membrane response of rabbits. Four groups were given either (a) no preexposure of the to-be-CS, (b) preexposure, (c) preexposure overlapped by hippocampal stimulation or (d) preexposure overlapped by cortical stimulation, followed by 300 conditioning trials for each group. After conditioning, the hippocampal group was divided into two groups designated HS-1 and HS-2 by means of a post-hoc test for stimulation effects. Conditioning was found to be retarded in all three preexposed groups, with significantly greater retardation (augmentation of latent inhibition) in Group HS-2. The results support a general conception that the hippocampal stimulation produced its effects through the modulation of sensory input.

Animals↗

Morphine withdrawal in mice selectively bred for differential sensitivity to ethanol.

Mice which have been selectively bred for differences in sensitivity to acute doses of alcohol have also been shown to differ in severity of seizures upon withdrawal from chronic alcohol administration. We investigated the responsiveness of these mice to withdrawal from chronic morphine treatment. Mice were made dependent on morphine via pellet implantation, and withdrawal was precipitated with naloxone challenge. Mice which are less sensitive to the hypnotic effects of ethanol (short sleep: SS) displayed more jumping and wet dog shakes during withdrawal than did the more sensitive long sleep (LS) mice. In addition, the amount of jumping was dependent on the dose of naloxone in both lines. Differences between lines in naloxone precipitated withdrawal may reflect differences in alterations in extrapyramidal dopaminergic activity, but other substrates for the observed differences cannot be discounted. Finally, the observed difference between SS and LS mice in severity of morphine withdrawal parallels the previously reported difference between these lines in seizure severity during withdrawal from alcohol.

Alcoholism↗

Attenuation of latent inhibition by electrical stimulation of hippocampus.

The effects of hippocampal stimulation on the development and expression of latent inhibition were investigated employing classical conditioning of the nictitating membrane response of rabbits. Hippocampal stimulation overlapping conditioned stimulus preexposure produced attenuation of latent inhibition, as did stimulation presented during conditioning after preexposure. However, hippocampal stimulation during conditioning in the absence of preexposure had little effect. The results support the hypotheses that in classical conditioning a major function of the hippocampus is the modulation of sensory input, especially input involved in the learned irrelevance of stimuli.

Animals↗