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Biomedical subjects

M E Trulson

Publications and source records attributed to M E Trulson.

123 records · Page 7Linked to original sources
PubMed1976

An animal behavior model for studying the actions of LSD and related hallucinogens.

Cats injected with LSD (d-lysergic acid diethylamide) exhibit a group of behaviors that appear to be specific to hallucinogenic drugs. Two of these behaviors, limb flick and abortive grooming, have an extremely low frequency of occurrence in normal cats, but often dominate the behavior of LSD-treated cats. The frequency of occurrence of this group of behaviors is related to the dose of LSD. The behavioral changes are long-lasting following a single injection of LSD, and exhibit tolerance following the repeated administration of LSD. They are not elicited by a variety of control drugs, but are elicited by other indole nucleus hallucinogens. Because the behavioral effects are specific, reliable, easy to score, and quantifiable, they represent an animal model that can be used in studies of the effects of LSD and related hallucinogens.

Animals↗
PubMed1976

Behavioral evidence for the rapid release of CNS serotonin by PCA and fenfluramine.

Administration of p-chloroamphetamine (PCA) (2.5-10.0 mg/kg) or fenfluramine (FF) (5.0-15.0 mg/kg) to rats induces a behavioral syndrome--consisting of tremor, rigidity, Straub tail, hindlimb abduction, lateral head weaving and reciprocal forepaw treading--which is a reflection of the activity of central serotonin-mediated synapses. The syndrome appears within 3-5 min following i.p. administration of PCA or FF, and the syndrome-inducing effects of PCA and FF are blocked by prior depletion of serotonin with p-chlorophenylalanine. By contrast, the syndrome-inducing effect of 5-methoxy-N,N-dimethyltryptamine (5-M-DMT), which directly stimulates postsynaptic serotonin receptors, is not changed by prior serotonin depletion. Catecholamine depletion with alpha-methyl-p-tyrosine produces essentially no change in the syndrome-inducing effects of PCA, FF or 5-M-DMT. These data indicate that the initial effect of PCA or FF administration is the rapid functional release of stored serotonin.

Amphetamines↗
PubMed1976

LSD acts synergistically with serotonin depletion: evidence from behavioral studies in cats.

Administration of LSD (100 mug/kg, IP) or the serotonin depleting drug p-chlorophenylalanine (150 mg/kg/day for 5 days) both induce dramatic behavioral changes which include the common stereotyped responses of rapid flicking movements of the limbs and abortive attempts at grooming. The combined action of LSD and p=chlorophenylalanine results in a marked increase in the occurrence of these behaviors, suggesting that LSD acts synergistically with serotonin depletion. These data therefore support the hypothesis that the behavioral effects of LSD may be attributable to its well known electrophysiological effect of depressing the activity of serotonin containing neurons. In addition, limb flicking and abortive grooming may serve as a useful behavioral model for studying the actions of LSD, since these behaviors are quantifiable, easily scored, and occur with an extremely low frequency in normal cats.

Amphetamine↗
PubMed1976

Biological bases for the integration of appetitive and consummatory grooming behaviors in the cat: a review.

Cats with pontile lesions, frontal neocortical lesions, and thyroidectomized cats display a dissociation of the appetitive and consummatory components of grooming behavior following tactile stimulation of the body surface, an abnormal behavior which waxes and wanes with the seasons of the year. Tryptophan hydroxylase activity and serotonin levels were significantly decreased in the superior colliculi (but not other brain regions) in cats with pontile lesions or frontal neocortical lesions, but not in thyroidectomized cats. Systemic administration of 5-hydroxytryptophan or monoamine oxidase inhibition plus tryptophan administration abolishes the abnormal grooming behavior in each group of cats, and microinjections of 5-hydroxytryptophan or serotonin into the superior colliculi has the same effect, indicating that the change in a serotonergic system is a critical aspect of the abnormal behavior in cats with lesions and that a serotonergic system may also be involved in the genesis of the abnormal grooming behavior in thyroidectomized cats. Functional inactivation of the serotonergic system by p-chlorophenylalanine, LSD, or serotonin receptor blockade does not induce the abnormal grooming behavior in normal cats, indicating that other factors are involved. Cats with lesions and thyroidectomized cats display a rhythmic dysfunction in the excretion of glucocorticoids and glucocorticoid administration abolishes the abnormal grooming behavior, suggesting that glucocorticoids are the other critical factor. Adrenalectomized cats do not display the abnormal grooming behavior, but when adrenalectomized cats are treated with p-chlorophenylalanine, the abnormal behavior appears. Thus, a serotonergic system in the superior colliculi, operating at some level of glucocorticoid function, is involved in the integration of appetitive and consummatory grooming behaviors.

5-Hydroxytryptophan↗
PubMed1976

Similarities in the physiological bases of an abnormal grooming behavior in thyroidectomized cats and in cats with lesions of the central nervous system.

Thyroidectomized cats display a dissociation of the appetitive and consummatory components of grooming behavior when the body surface is tactually stimulated, an abnormal behavior that also occurs in cats with pontile or frontal neocortical lesions. Systemic administration of 5-hydroxytryptophan (5-HTP) abolishes the abnormal behavior, whereas dihydroxyphenylalanine administration does not, and p-chlorophenylalanine (PCPA) administration induces the abnormal grooming behavior in thyroidectomized cats that are not displaying the abnormal behavior because of spontaneous seasonal reversions. Microinjections of 5-HTP or serotonin into the superior colliculi also abolish the abnormal grooming behavior in thyroidectomized cats. Lesions of the superior colliculi prevent the development of the abnormal behavior after thyroidectomy, even with PCPA treatment. These pharmacological results in thyroidectomized cats parallel the behavioral effects observed in cats with pontile or frontal neocortical lesions.

Animals↗
PubMed1976

Behavioral evidence for supersensitivity following destruction of central serotonergic nerve terminals by 5,7-dihydroxytryptamine.

Previous studies have established that a complex behavioral syndrome--consisting of tremor, rigidity, hindlimb abduction. Straub tail, lateral head weaving and reciprocal forepaw treading--is a specific reflection of the activity of central serotonin receptors. This syndrome was utilized in the present study to test for supersensitivity in the central serotonergic system. Specific destruction of central serotonin nerve terminals by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT, 50 mug) in adult male rats pretreated with a catecholamine uptake blocking agent resulted in marked supersensitivity to serotonin precursors and agonists. The greatest degree of supersensitivity was observed in response to L-5-hydroxytryptophan, for which the ED50 for elicitation of the syndrome was 20% of the value for control rats. A lesser degree of supersensitivity was seen in response to L-tryptophan (following monoamine oxidase inhibition) and the direct-acting serotonin agonist, 5-methoxy-N,N-dimethyltryptamine, for which the ED50 was approximately 50% of the control value in both cases. Supersensitivity begins to develop within 24 hours and is relatively complete by 96 hours after 5,7-DHT. A marked subsensitivity to the serotonin releasing agent, fenfluramine, was found in 5,7-DHT-treated rats. In contrast to the marked supersensitivity to serotonin precursors and agonists which occurs following 5,7-DHT, chronic administration of a serotonin synthesis inhibitor, p-chlorophenylalanine (400 mg/kg every 3 days for a total of 24 days), did not produce supersensitivity to L-5-hydroxytryptophan or 5-methoxy-N,N-dimethyltryptamine. Possible pre- and postsynaptic mechanisms for the development of supersensitivity are discussed.

5-Hydroxytryptophan↗
PubMed1976

Behavioral evidence for the stimulation of CNS serotonin receptors by high doses of LSD.

Systemic administration of lysergic acid diethylamide (LSD) to rats induces a behavioral syndrome--consisting of tremor, rigidity, Straub tail, hindlimb abduction, lateral head weaving and reciprocal forepaw treading--which is a reflection of increased activation of central serotonin receptors. Utilizing this behavioral measure, a marked supersensitivity to LSD was observed in rats whose serotonin nerve terminals had been selectively destroyed, and a dramatic tolerance to LSD was observed following its repeated administration to normal rats. These data provide direct evidence that LSD can stimulate CNS serotonin receptors to a degree which markedly affects behavior.

Animals↗
PubMedDate not supplied

Role of limbic system in the control of hamster growth.

Rostral septal lesions accelerate somatic growth in adult hamsters. This study tested the hypothesis that this effect results from damage to fibers of passage by observing the effects of transections of septohippocampal and septohypothalamic connections on growth. We attempted to identify these fibers further by (a) measuring spectrofluorometrically changes in the monoamine concentrations in hippocampus, cerebral cortex, corpus striatum, and diencephalon, (b) staining the degenerating axons after septal lesions and the two cuts, and (c) examining the correspondence between such damage and the acceleration of growth. Both knife cuts accelerated somatic growth and were associated (as well as septal lesions) with significant depletions of serotonin (-27 to -57%) and norepinephrine (-27 to -60%) in the hippocampus, with less consistent depletions of these monoamines in the cerebral cortex, and with no changes in regional dopamine content. All three procedures were associated with degeneration in the hippocampal formation and its fiber systems. Thus, fibers interconnecting hippocampus and brainstem, and passing through septum, exert tonic suppression over somatic growth in adult hamsters.

Animals↗