Biomedical subjects

M E Trulson

Publications and source records attributed to M E Trulson.

At least 37 records · Page 2Linked to original sources

PubMed1986

Do serotonin-containing dorsal raphe neurons possess autoreceptors?

The potential role of autoreceptors in regulating the activity of serotonin-containing dorsal raphe (RD) neurons was examined by recording the activity of these neurons under a variety of conditions both in vivo and in vitro in the mouse. RD neurons recorded in vivo displayed the characteristic slow, rhythmic discharge pattern previously described for rat and cat RD cells. The activity of these neurons was suppressed in a dose-dependent manner by tryptophan, LSD and chlorimipramine administered intravenously. The inhibitory effect of tryptophan and chlorimipramine was abolished by pretreatment with p-chlorophenylalanine, while that of LSD was not. 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. Prior depletion of brain serotonin by p-chlorophenylalanine administration resulted in no significant change in RD neuron activity recorded in vitro. Elevation of brain serotonin by monoamine oxidase inhibition produced a total suppression of raphe cell 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 RD neuron activity. This depressant effect of serotonin was rapidly reversible upon drug wash-out. Serotonin receptor blockers, methiothepin, cyproheptadine and methysergide produced no significant change in RD cell activity. The 5HT reuptake blocker, fluoxetine, produced a total suppression of RD neuron activity in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1986

Chronic cocaine administration depletes tyrosine hydroxylase immunoreactivity in the rat brain nigral striatal system: quantitative light microscopic studies.

Chronic administration of cocaine (10 mg/kg, i.p., every 12 h for 10 consecutive days) produced a large decrease in tyrosine hydroxylase-staining axons and terminal boutons in the caudate nucleus in rats when examined 60 days after the final cocaine injection. This effect was quantitated using the Leitz data acquisition and display system (DADS) which revealed that there was a 63% decrease in tyrosine hydroxylase-positive processes in the caudate nucleus. In addition, this cocaine treatment regimen produced a large decrease in the number of tyrosine hydroxylase-positive staining neuronal perikarya in the pars compacta of the substantia nigra. Use of the Leitz-DADS system revealed that there was a 51% decrease in tyrosine hydroxylase-positive material in the substantia nigra. These data demonstrated that chronic administration of cocaine produced a long-term loss of tyrosine hydroxylase in both the cell bodies of the substantia nigra and the nerve terminals of the caudate nucleus. Further studies are required to determine whether the observed changes are due to degeneration of the neurons or some metabolic effect.

Animals↗

PubMed1986

Buspirone decreases the activity of serotonin-containing neurons in the dorsal raphe in freely-moving cats.

Buspirone, a non-benzodiazepine anxiolytic agent, produced a dose-dependent decrease in the activity of serotonin-containing neurons in the dorsal raphe nucleus of freely-moving cats. The response ranged from no significant change at doses of 0.05 mg/kg to a nearly total suppression of activity at 1 mg/kg. These data suggest that the anxiolytic properties of buspirone may be mediated, at least part, by an action on neurons in the dorsal raphe.

Animals↗

PubMed1986

Dissociations between the effects of hallucinogens on behavior and raphe unit activity in behaving cats.

The hypothesis that hallucinogenic drugs exert their behavioral effects by an action at pre- or postsynaptic serotonin receptors was evaluated by co-administering various drugs that possess either serotonin agonist or antagonist properties, while concurrently monitoring behavior and the electrophysiological activity of serotonin-containing dorsal and median raphe neurons in freely moving cats. Co-administration of the serotonin receptor blockers, metergoline or mianserin, with lysergic acid diethylamide (LSD) produced no change in the inhibitory effects of LSD on raphe neurons, but produced a dose-dependent blockade of the behavioral effects of LSD in the cat. The latter data suggest that perhaps LSD exerts its behavioral effects by an action at postsynaptic serotonin receptors. Co-administration of drugs that increase synaptic serotonin, L-5-hydroxytryptophan, tranylcypromine, fluoxetine or p-chloramphetamine with LSD greatly potentiated the inhibitory effect of LSD on raphe unit activity, but also produced dose-dependent decreases in these behavioral effects of LSD in the cat. Thus, both enhancing the activity at postsynaptic serotonin receptors and receptor antagonism blocked the behavioral effects of LSD. Co-administration of dopamine receptor blockers, haloperidol or chlorpromazine, produced no significant change in the response of raphe neurons to LSD, but these drugs also produced a dose-dependent blockade of the behavioral effects of LSD in the cat. Co-administration of the dopamine agonists, apomorphine or d-amphetamine, however, potentiated the behavioral effects of LSD, while producing a partial reversal of the inhibitory effects of LSD on raphe unit activity. The results are discussed in the context of using animal models to study the possible actions of hallucinogens in humans.

Animals↗

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.

Animals↗

PubMed1986

Serotonin neuron transplants: electrophysiological unit activity of intrahippocampal raphe grafts in freely moving cats.

Fetal serotonin (5HT)-containing neurons from the cat midbrain raphe were transplanted to the hippocampus of adult host cat brain. These neurons displayed spontaneous electrophysiological activity in freely moving cats, and showed the pacemaker-like discharge pattern characteristic of these cells. However, these neurons showed no significant change in activity across the sleep-waking cycle, nor were they responsive to sensory stimulation in the auditory and visual modalities. Grafted neurons were inhibited by 5HT agonists, but required higher doses than those in intact cats. These data are the first electrophysiological recordings of grafted 5HT neurons in freely moving animals, and question whether such tissue grafts can restore functional activity in the central 5HT system.

Acoustic Stimulation↗

PubMed1986

Ultrastructural changes of the liver following L-tryptophan ingestion in rats.

Oral administration of L-tryptophan at 250 mg/(kg X d) for 3 consecutive days to rats produced enlarged hepatic sinusoids and vacuolated cells, many of which contained lipid. These changes persisted for at least 2 wk. Since the hepatic metabolism of L-tryptophan is very similar in rats and humans, these data suggest that people who self-administer large doses of L-tryptophan for the purpose of decreasing sleep latency may be inducing hepatic pathology.

Animals↗

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↗

PubMed1986

Buspirone decreases the activity of 5-hydroxytryptamine-containing dorsal raphe neurons in-vitro.

Buspirone, a non-benzodiazepine anxiolytic agent, produced a dose-dependent decrease in the activity of 5-HT-containing dorsal raphe neurons recorded from mouse brain slices. The response was not changed in a low calcium/high magnesium incubation medium, indicating that the observed effects were the result of a direct action of buspirone on raphe neurons. These data are discussed within the context of the anxiolytic effects of buspirone.

Animals↗

PubMed1986

Effects of methamphetamine on arterioles of rat caudate nucleus and midbrain.

No differences in arteriolar metabolic profiles from rat caudate nucleus, ventral tegmental area or substantia nigra were observed between saline-control and methamphetamine HCl-treated (20 mg/kg, i.p. twice daily for 10 consecutive days) animals. Arterioles from the above regions of forebrain and midbrain are metabolically active vessels with a capacity for aerobic and anaerobic metabolism. These results suggest that a high dose of methamphetamine does not alter cerebral arteriolar metabolism in the areas examined.

Animals↗

PubMed1985

Simultaneous recording of dorsal raphe unit activity and serotonin release in the striatum using voltammetry in awake, behaving cats.

Simultaneous recordings of unit activity in the dorsal raphe nucleus (RD) and serotonin (5HT) release in the striatum were made in the cat. Unit recordings were made using Formvar-coated 32 microns diameter nichrome wires. 5HT release was measured using linear sweep voltammetry with semi-differentiation using electrodes prepared from Teflon-coated 32-gauge stainless steel wire filled with carbon paste and Ag/AgCl electrodes and 27-gauge stainless steel needles as reference and auxiliary electrodes, respectively. The working electrodes were scanned at a rate of 10 mV/s over the range of -0.1 to +0.5 V every 5 minutes using a BAS CV37 voltammograph. During REM sleep RD unit activity was decreased 94% from quiet waking (QW) baseline, while the voltammetric response was decreased by only 57%. Chloral hydrate anesthesia decreased RD unit activity by 18% from QW while the voltammetric response was decreased by 39%. LSD decreased RD unit activity by 50% from QW, but the voltammetric response was decreased by 88%. P-chlorophenylalanine produced no significant change in RD unit activity but decreased the voltammetric response by 82%. These data suggest that RD unit activity and 5HT release often differed dramatically.

Animals↗

PubMed1985

Chronic administration of D-amphetamine increases [3H]spiroperidol binding in cat brain.

Administration of D-amphetamine sulfate twice daily for 10 consecutive days, in doses increasing from 10 mg/kg per day (i.p.) to 30 mg/kg per day resulted in significant increases in the Bmax for [3H]spiroperidol receptor binding in the striatum (+44.7%) and limbic forebrain (+40.3%) in cats. There were no significant changes in the KD value for either brain region. A single dose of amphetamine (15 mg/kg i.p.) produced no significant changes in [3H]spiroperidol binding in either brain region. These data are in contrast with previous studies which reported a significant decrease in dopamine receptor binding following chronic amphetamine treatment in rats.

Animals↗

PubMed1985

A metabolic profile of the rat caudate microvasculature: a histochemical study.

Arterioles of the rat caudate nucleus were examined histochemically to determine their metabolic profile. These microvessels appear capable of aerobic and anaerobic metabolism with a potential for nucleic acid and protein synthesis. Little intramural lipid storage occurs and any fatty acids utilized are provided via the blood supply. Likewise, glycogen is not seen in the arteriolar wall and may be rapidly turned over as a substrate for anaerobic metabolism.

Animals↗

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.

Action Potentials↗

PubMed1985

Morphine increases the activity of midbrain dopamine neurons in vitro.

Morphine produced a dose-dependent increase in the activity of dopamine-containing neurons in the substantia nigra and ventral tegmental area recorded from mouse brain slices in vitro. The response was not changed in a low calcium/high magnesium incubation medium, indicating that the observed effects are the result of the direct action of morphine on dopamine neurons. Furthermore, a specific opiate antagonist, naloxone, reversed the excitatory effects of morphine in both brain regions, while naloxone alone had no significant effect on the activity of dopaminergic neurons. Morphine was more potent on ventral tegmental area than substantia nigra dopamine neurons. beta-Endorphin excited ventral tegmental area neurons but not substantia nigra cells, while [Leu5]enkephalin activated cells in both nuclei. These latter responses were blocked by naloxone. These data suggest that midbrain dopamine neurons contain receptors for opiates, and that ventral tegmental area neurons are more sensitive to the action of opiates than substantia nigra neurons.

Animals↗

PubMed1985

Separation of tolerance to the behavioral effects of LSD from changes in serotonin receptor binding in cats.

Nearly complete tolerance to a test dose of 50 micrograms/kg of LSD occurred within 24 h following an initial dose of 50 micrograms/kg of the drug, using limb flicking and abortive grooming as as behavioral indices in the cat. No changes in serotonin receptor binding were observed at this time. However, chronic administration of LSD (50 micrograms/kg every 12 h for 6 days) produced a significant decrease in serotonin receptor binding in both the forebrain and brainstem plus spinal cord. These data suggest that the behavioral effects of LSD and tolerance to LSD as measured here are mediated predominantly by different sites.

Animals↗

PubMed1985

Development of tolerance to repeated administration of 5-methoxy-N,N-dimethyltryptamine in rats.

Chronic administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 2 mg/kg i.p., every 30 min for 4 h) produced a dramatic tolerance to the behavioral effects of the drug in rats. The ED50 for the syndrome-inducing effects of the drug was increased from 1.3 to 2.4 mg/kg, and the mean duration of the syndrome was decreased from 14.9 to 1.2 min after this treatment. This tolerance effect totally disappeared within 4 h following termination of drug treatment. This effect was not due to changes in the uptake of 5MeODMT into the brain, but rather appears to be due to a decrease in the binding of the drug to serotonin receptors in the central nervous system. These studies are in contrast to previous results which reported no development of tolerance to 5-MeODMT.

Animals↗

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↗