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Biomedical subjects

M E Trulson

Publications and source records attributed to M E Trulson.

At least 19 recordsLinked to original sources
PubMed1987

A comparison of the electrophysiological and pharmacological properties of serotonin-containing neurons in the nucleus raphe dorsalis, raphe medianus and raphe pallidus recorded from mouse brain slices in vitro: role of autoreceptors.

The potential role of autoreceptors in regulating the activity of serotonin-containing nucleus raphe dorsalis (RD), raphe medianus (RM) and raphe pallidus (RPA) neurons was examined by recording the activity of these neurons under a variety of conditions both in vivo and in vitro. Raphe neurons recorded in vivo displayed the characteristic slow, rhythmic discharge pattern previously described for rat and cat raphe cells. The activity of these neurons was suppressed in a dose-dependent manner by tryptophan, LSD and chlorimipramine administered intravenously. There were no significant changes in the spontaneous discharge rate of raphe neurons over time when recorded in vitro, even though tissue serotonin and its metabolite, 5-hydroxyindoleacetic acid, decreased dramatically. RPA neurons fired significantly faster than either RD or RM neurons both in vivo and in vitro. Prior depletion of brain serotonin by p-chlorophenylalanine administration resulted in no significant change in raphe unit activity recorded in vitro. Elevation of brain serotonin by monoamine oxidase inhibition produced a total inhibition of raphe unit activity in vitro. Similarly, increasing the concentration of serotonin in the tissue slice by adding serotonin directly to the incubation medium resulted in a profound, though transitory, depression of unit activity. This depressant effect of serotonin was rapidly reversible upon drug wash-out. Serotonin receptor blockers, methiothepin, cypoheptadine, and methysergide, produced no significant change in unit activity. The serotonin reuptake blocker, fluoxetine, produced a total inhibition of raphe unit activity in all three nuclei in vitro. These data suggest that excess serotonin suppresses the activity of raphe neurons, apparently by an action on autoreceptors, but that a deficiency, or normal concentration, of serotonin does not influence the spontaneous activity of these cells. The data also show that RD and RM are much more sensitive to the depressant effects of serotonin than the caudal RPA neurons. More generally, these studies provide a data base for examining the electrophysiological and pharmacological characteristics of serotonergic neurons in the three major serotonin-containing nuclei in mouse brain. The mouse has proven to be a much easier species than the rat to use in these types of studies, based on the finding that mouse brain slices are more viable in vitro than are rat brain slices.

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PubMed1986

Effects of elevated calcium on learned helplessness and brain serotonin metabolism in rats.

The effects of elevated calcium on learned helplessness in rats was tested by maintaining animals on either distilled water or water containing 2.5% calcium. Animals that were maintained on drinking water containing high calcium showed elevated levels of brain and serum calcium. Rats that were maintained on high calcium drinking water showed significantly longer escape latencies than their non-calcium counterparts after they were pretreated with inescapable electric shocks. Lower levels of 5-hydroxyindoleacetic acid (5HIAA) were found in the forebrain and brainstem of animals maintained on high calcium drinking water. There was no significant correlation between blood or brain calcium or 5HIAA levels and latency of escape. We conclude that elevated levels of calcium enhance learned helplessness and decrease brain serotonin turnover. The relationship between depressive states and calcium homeostasis is worthy of further investigation.

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PubMed1986

Streptozotocin-induced diabetes reduces brain serotonin synthesis in rats.

The rate of brain 5-hydroxytryptamine (serotonin) synthesis and turnover in streptozotocin-diabetic rats was assessed using three separate methods: the rate of 5-hydroxytryptophan accumulation following decarboxylase inhibition with Ro 4-4602; the decline in 5-hydroxyindoleacetic acid levels following monoamine oxidase inhibition with pargyline; and the rate of 5-hydroxyindoleacetic acid accumulation following blockade of acid transport with probenecid. Each of the three methods revealed that 5-hydroxytryptamine synthesis and turnover is decreased by 44-71% in diabetic rats with plasma glucose levels of between 500 and 600 mg%. In addition, the levels of free and bound plasma tryptophan were measured and the levels of the free amino acid were found to be the same in control and diabetic rats. Since diabetic rats exhibit a 40% decrease in brain tryptophan, the free tryptophan level in plasma does not predict brain tryptophan levels in diabetic rats. These data are discussed within the context of psychiatric disturbances experienced by diabetic patients.

5-Hydroxytryptophan↗
PubMed1985

Dietary tryptophan does not alter the function of brain serotonin neurons.

The hypothesis that alterations in dietary tryptophan modify the functional activity of brain serotonin-containing neurons was tested by recording the electrophysiological activity of single serotonergic cells in awake, behaving cats after meal ingestion of diets containing varying proportions of tryptophan and the neutral amino acids that compete with tryptophan for uptake into the brain. The data revealed that while the various diets produced significant changes in brain serotonin and its major metabolite, 5-hydroxyindoleacetic acid, there was no change in the activity of serotonin-containing dorsal raphe cells following meal ingestion. Furthermore, a pulse injection of tritiated labeled tryptophan following the various diets produced no significant change in the release of tritiated serotonin into the lateral ventricles, while tritiated 5-hydroxyindoleacetic acid was significantly increased. These data suggest that dietary tryptophan does not alter the functional activity of central serotonergic neurons, in contrast with current popular beliefs that such dietary manipulations alter brain function.

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PubMed1985

Unit activity in the dorsal raphe in freely-moving cats. Effect of monoamine oxidase inhibitors.

Two commonly used monoamine oxidase inhibitors, tranylcypromine and pargyline, produced dose-dependent decreases in the activity of serotonin-containing neurons in the dorsal raphe in awake, freely-moving cats. The onset of the suppression of unit activity occurred within 15-20 min after administration of drug and persisted for 6-16 hr, depending upon dose. Parallel neurochemical studies revealed that serotonin in the brain was significantly increased following inhibition of monoamine oxidase, and that concentrations of serotonin were still significantly elevated after unit activity in the raphe had returned to baseline levels. These data suggest that autoreceptors on neurons of the dorsal raphe may become tolerant following prolonged exposure to large concentrations of serotonin.

Animals↗
PubMed1985

Calcium regulates the activity of serotonin-containing dorsal raphe neurons in vitro.

Small elevations of calcium ions (15%) significantly depressed the activity of serotonin-containing dorsal raphe neurons by 35% in mouse brain slices in vitro, while large increases in calcium ion concentration (300%) dramatically decreased the incidence of spontaneously active raphe neurons. Neurochemical studies indicated that these effects were not attributable to increased release and metabolism of serotonin. These findings may have implications for the treatment of mood disorders, for which disturbances in both calcium and serotonin metabolism have been demonstrated.

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PubMed1979

Long-term amphetamine treatment decreases brain serotonin metabolism: implications for theories of schizophrenia.

Long-term amphetamine administration to cats (a mean of 8.75 milligrams per kilogram twice daily for 10 days) produced large decreases (40 to 67 percent in serotonin and its major metabolite, 5-hydroxyindoleacetic acid, in all brain regions examined. This treatment also produced several behaviors that are dependent on depressed central serotonergic neurotransmission, and which normally are elicited exclusively by hallucinogenic drugs. Short-term amphetamine administration (15 mg/kg) did not produce these behaviors and resulted in small decreases in brain serotonin and no change in 5-hydroxyindoleacetic acid. These data are discussed in the context of monoamine theories of schizophrenia.

Animals↗
PubMed1979

Dissociations between the effects of LSD on behavior and raphe unit activity in freely moving cats.

The hypothesis that the action of hallucinogenic drugs is mediated by a depression of the activity of brain serotonergic (raphe) neurons was tested by examining the behavioral effects of d-lysergic acid diethylamide (LSD) while studying the activity of raphe neurons in freely moving cats. Although the results provide general support for the hypothesis, there were several important dissociations. (i) Low doses of LSD produced only small decreases in raphe unit activity but significant behavoiral changes; (ii) LSD-induced behavioral changes outlasted the depression of raphe unit activity; and (iii) raphe neurons were at least as responsive to LSD during tolerance as they were in the nontolerant condition.

Animals↗
PubMed1979

Raphe unit activity in freely moving cats: correlation with level of behavioral arousal.

Dorsal raphe unit activity in freely moving cats showed a slow, rhythmic discharge rate during quiet waking (X=2.82 +/- 0.17 spikes/sec), and displayed a strong positive correlation with level of behavioral arousal. Presentation of an auditory stimulus during quiet waking resulted in significant increases in unit activity of 112% and 39% during the first sec and first 10 sec after the stimulus, respectively. This effect rapidly habituated with repeated stimulus presentations. During active waking, unit activity was significantly increased by 22% as compared to quiet waking, but there was no correlation between unit activity and gross body movements. Raphe unit activity showed a significant decrease of 17% during drowsiness (first appearance of EEG synchronization) as compared to quiet waking, and then progressive decreases during the early (--34%), middle (--52%) and late (--68%) phases of slow wave sleep. During all phases of slow wave sleep, the occurrence of sleep spindles was frequently associated with a transitory decrease in unit activity. The discharge rate would typically decrease during the few seconds immediately preceding the spindle, remains at this low level during the occurrence of the spindle, and then increase immediately after the spindle. Raphe unit activity showed decreases of 81% during pre-REM (the 60 sec immediately before REM onset) and 98% during REM, as compared to quiet waking. Unit activity reappeared 3.2 sec before the end of REM, with significant increases in unit activity of 83% and 17% during the first sec and first 10 sec of unit activity, respectively, as compared to quiet waking. The results of these studies are discussed in relation to the hypothesis that serotonin may play a modulatory, rather than mediative, role in behavioral and physiological processes.

Animals↗
PubMed1979

Effects of 5-methoxy-N,N-dimethyltryptamine on behavior and raphe unit activity in freely moving cats.

5-methoxy-N,N-dimethyltryptamine (5-MeODMT) produced a dose-dependent decrease in the discharge rate of serotonin-containing neurons in the dorsal raphe nucleus of freely moving cats. This ranged from a 15% decrease at 10 microgran/kg, i.m., to a virtual complete depression of activity at 250 microgram/kg. 5-MeODMT's effects on raphe units occurred with a very short latency (3-5 min) and its duration of action was dose-dependent and limited to an hour or less. The degree of depression of raphe unit activity was directly related to the frequency of occurrence of a number of hallucinogen-specific cat behaviors such as limb flick and abortive groom. There was also a close temporal correlation between the depression of raphe unit activity and the occurrence of these behaviors. These data indicate that the effects of 5-MeODMT may be primarily dependent on its actions upon brain serotonin neurons.

Animals↗
PubMed1979

Hyperphagia following intraventricular p-chlorophenylalanine-, leucine- or tryptophan-methyl esters: lack of correlation with whole brain serotonin levels.

The methylester hydrochlorides of DL-p-chlorophenylalanine (PCPA), L-leucine and L-tryptophan were intraventricularly administered to rats. All compounds produced increased food intake compared to saline administration. PCPA and leucine administration significantly decreased serotonin levels by 15--18%, while no serotonin depletion occurred following tryptophan injections. The data suggest that intraventricular injections of large quantities of neutral amino acid methyl esters may cause hyperphagia in rats through non-serotonergic effects on brain function.

Animals↗
PubMed1979

Chronic amphetamine administration to cats: behavioral and neurochemical evidence for decreased central serotonergic function.

Chronic administration of amphetamine to cats (twice daily, in doses increasing from 5 to 15 mg/kg over a 10-day period) elicited a number of behaviors, e.g., limb flick and abortive groom, characteristic of the action of hallucinogenic drugs and dependent on a depression of central serotonergic neurotransmission. This drug treatment produced large decreases (-40 to -60%) in central nervous system serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), when measured either 6 or 24 hr after the last amphetamine injection. The rate of limb flicking returned to a predrug level approximately 5 days after drug withdrawal, at which time 5-HT and 5-HIAA levels had returned to within 30 to 40% of base line. Both 5-HT and 5-HIAA returned to base-line levels within 14 days after drug withdrawal. Norepinephrine (NE), dopamine (DA) and DA metabolites were decreased 60 to 95% by chronic amphetamine treatment and showed little recovery within the 14 days after drug withdrawal. A second experiment examined the latency to onset of the behavioral and neurochemical changes with a constant dose of amphetamine (7.5 mg/kg, twice daily). Limb flicking was significantly increased above base-line levels following 3 days of amphetamine administration, at which time 5-HT and 5-HIAA levels were decreased 30 to 40%. NE, DA and DA metabolites were decreased approximately 50 to 90% by this treatment regimen. A third experiment examined the effects of a low dose of amphetamine (3.75 mg/kg), injected more frequently (every 6 hr for 6 days), to approximate the administration pattern in human amphetamine abuse. This treatment produced significant increases in limb flicking and abortive grooming on days 5 and 6 and resulted in 30 to 40% depletions of 5-HT and 5-HIAA. NE, DA and DA metabolites were decreased by approximately 50 to 90%. These data are discussed in relation to a role for serotonin in amphetamine psychosis and schizophrenia.

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