Biomedical subjects

M E Trulson

Publications and source records attributed to M E Trulson.

At least 55 records · Page 3Linked to original sources

PubMed1985

Activity of dopamine-containing substantia nigra neurons in freely moving cats.

The present series of studies examined the activity of presumed dopamine-containing neurons in the substantia nigra of freely moving cats. These neurons were found to have a slow (1-9 spikes/sec) discharge rate, unusually long duration action potentials (2-4 msec) and frequently fired in bursts with progressive decreases in the amplitude of the action potential within the burst. These neurons showed no significant change in their activity across the sleep-waking cycle, and showed no changes in activity with phasic movement. Most units were unresponsive to olfactory, noxious, tactile, auditory and visual stimulation, when unit activity was integrated over several seconds following stimulus presentation. However, phasic auditory and visual stimuli produced a period of excitation lasting approximately 120 msec after a delay of about 80 msec. The period of excitation was followed by a period of inhibition lasting approximately 60 msec. Presumed dopamine-containing substantia nigra units showed no significant circadian changes in activity. The firing rates of these units were inhibited by dopamine agonists, including the direct-acting agonist, apomorphine, the dopamine precursor, L-dihydroxyphenylalanine, a dopamine releasing agent, d-amphetamine, and a dopamine reuptake blocker, bupropion, and were excited by a dopamine receptor blocker, haloperidol. Thus, these neurons show many similarities to dopamine units recorded in anesthetized rats; however, they showed several notable differences as well. Recording the activity of these units in behaving animals allows one to examine behavioral correlates of unit activity. Furthermore, the data (sensory stimulation, pharmacological, etc.) obtained in the unanesthetized preparation are far more relevant to the physiological and pharmacological effects that may occur in humans.

Action Potentials↗

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.

Action Potentials↗

PubMed1985

Simultaneous recording of substantia nigra neurons and voltammetric release of dopamine in the caudate of behaving cats.

Simultaneous electrophysiological recordings of single dopamine-containing neurons in the pars compacta of the substantia nigra and the voltammetric release of dopamine in the caudate were made in the behaving cat. Unit activity showed no significant changes during sleep and small changes during active waking, while the release of dopamine in post-synaptic target regions of the caudate nucleus decreased by approximately 35% during sleep and increased approximately 50% during movement. These data demonstrate that recording the electrophysiological activity of single dopamine-containing neurons alone does not accurately reflect the functional state of the central dopamine system. The present study is the first report on the simultaneous measurement of the post-synaptic release of a neurotransmitter and the electrophysiological recording of neurons identified to contain that transmitter substance.

Animals↗

PubMed1985

Identification of dopamine-containing cell bodies in the dorsal and median raphe nuclei of the rat brain using tyrosine hydroxylase immunochemistry.

Using immunohistochemical methods with antibodies specific to tyrosine hydroxylase, we examined the distribution of dopaminergic cells in the dorsal and median raphe nucleus of the rat brain. Although dopamine-containing cell bodies were previously thought to be almost exclusively confined to the substantia nigra pars compacta, ventral tegmental area, and tuberoinfundibular system, we found numerous cell bodies which stained for tyrosine hydroxylase in the dorsal and median raphe nuclei.

Animals↗

PubMed1985

Effects of chronic methamphetamine on the nigral-striatal dopamine system in rat brain: tyrosine hydroxylase immunochemistry and quantitative light microscopic studies.

Chronic administration of methamphetamine (20 mg/kg, IP, every 12 hours for 10 days) produced a large decrease in tyrosine hydroxylase staining axons and terminal boutons in the caudate nucleus in rats when examined 60 days following the final methamphetamine injection. This effect was quantitated using the Leitz Data Acquisition and Display System (DADS) revealing that there was a 74% decrease in tyrosine hydroxylase positive processes in the caudate nucleus. Furthermore, this treatment also produced a large decrease in the number of tyrosine hydroxylase positive staining neuronal perikarya in the pars compacta of the substantia nigra. This effect was also quantitative using the Leitz-(DADS) system, revealing a decrease of 89% in tyrosine hydroxylase positive material. These data demonstrate that chronic administration of methamphetamine produces a long-term loss of tyrosine hydroxylase enzyme in both the cell bodies of the substantia nigra and the nerve terminals in the caudate nucleus. Whether this effect is due to the degeneration of the neurons or some metabolic effect remains to be determined.

Animals↗

PubMed1985

Effects of insulin and streptozotocin-induced diabetes on brain norepinephrine metabolism in rats.

Administration of insulin (2 IU/kg, i.p.) produced a significant decrease (18%) in forebrain norepinephrine and a significant increase in the major metabolite of norepinephrine, 3-methoxy-4-hydroxyphenylglycol-sulfate (MOPEG-SO4, +19%) in rats. Streptozotocin-induced diabetes produced the opposite effects, resulting in an increase in forebrain norepinephrine (+17%) and a decrease in MOPEG-SO4 (-26%). In addition, insulin increased (+143%) and diabetes decreased (-41%) the turnover rate of norepinephrine, as measured by the rate of decrease of norepinephrine following inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine. All of these effects in diabetic rats were reversed by insulin replacement therapy. These data are discussed within the context of mood disorders characteristic of diabetic patients.

Animals↗

PubMed1985

Ascorbic acid antagonizes the behavioural effects of LSD in cats.

Pretreatment with ascorbic acid (500 mg kg-1 i.p.) antagonized the behavioural effects of lysergic acid diethylamide (LSD) and apomorphine, but not 5-methoxy-N,N-dimethyltryptamine, in cats. The data support the hypothesis that these behavioural effects in cats are due to drug action at both 5-HT and dopamine receptors, and that the action of LSD at dopamine receptors is modulated by ascorbic acid.

Animals↗

PubMed1984

Buspirone increases locus coeruleus noradrenergic neuronal activity in vitro.

Buspirone, a non-benzodiazepine anxiolytic agent, produced dose-dependent increases in the activity of norepinephrine-containing locus coeruleus neurons 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 were the result of a direct action of buspirone on locus coeruleus neurons. These data suggest that noradrenergic neurons may not be as important in mediating anxiety states as previously suggested.

Action Potentials↗

PubMed1984

Role of norepinephrine in regulating the activity of serotonin-containing dorsal raphe neurons.

Previous studies have yielded conflicting results concerning the role of noradrenergic afferents to the dorsal raphe nucleus in regulating the activity of serotonergic neurons. In the present study, we recorded the activity of serotonin-containing dorsal raphe neurons in mouse brain slices in vitro under the following conditions: (a) no treatment, (b) phenylephrine added to the incubation medium, (c) in tissue obtained from mice that were anesthetized with halothane, (d) same condition as c, with phenylephrine added to the incubation medium, and (e) same as condition c, with the addition of bicuculline to the incubation medium. The data revealed that the neurons recorded with no treatment exhibited a spontaneous discharge rate of 3.40 +/- 0.29 spikes/sec and a cell/tract ratio of 1.15, while cells recorded from tissue slices obtained from halothane anesthetized mice exhibited a discharge rate of 2.01 +/- 0.27 spikes/sec and a cell/track ratio of 0.58. Addition of phenylephrine to the incubation media in slices obtained from anesthetized mice increased both the discharge rate (4.23 +/- 0.30 spikes/sec) and cell/tract ratio (1.28). Similarly, addition of bicuculline to the incubation media increased both the discharge rate (4.09 +/- 0.46 spikes/sec) and cell/tract ratio (1.21) in mouse brain slices obtained from anesthetized animals. Thus, we conclude that a noradrenergic input (which is removed in the tissue slice preparation) is not necessary to maintain the spontaneous activity of serotonergic dorsal raphe units. Halothane anesthesia depressed the activity of these neurons, presumably by releasing GABA from interneurons. Finally, while dorsal raphe neurons are not dependent upon an excitatory noradrenergic input to maintain their spontaneous activity, these neurons can be excited by noradrenergic afferents under certain conditions.

Animals↗

PubMed1984

Behavioral effects of serotonergic and dopaminergic drugs in cats following chronic amphetamine administration.

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 flicking, abortive grooming, and excessive head shaking, which were originally proposed as an animal behavioral model for studying the actions of hallucinogens that depress central serotonergic neurotransmission. This drug treatment produced large decreases (approximately 50%) in central nervous system serotonin (5HT) and its major metabolite, 5-hydroxyindoleacetic acid, and even larger decreases (approximately 90%) in the levels of dopamine (DA) and norepinephrine. Administration of the 5HT precursors L-tryptophan (25 mg/kg i.p.) or L-5-hydroxytryptophan (12.5 mg/kg i.p.), a direct-acting 5HT agonist (quipazine, 1 mg/kg i.p.) or a monoamine oxidase inhibitor (tranylcypromine, 4 mg/kg i.p.) produced no significant changes in these behaviors in cats treated chronically with amphetamine. Administration of a 5HT reuptake blocker (fluoxetine, 5 mg/kg i.p.) produced a small, but significant, decrease in the frequency of occurrence of these behaviors in amphetamine-treated cats. L-Dihydroxyphenylalanine (L-DOPA, 20 mg/kg i.p.) greatly potentiated these behaviors in cats chronically treated with amphetamine, but L-DOPA was totally ineffective in eliciting these behaviors in naive animals. The behavioral effects of apomorphine (2 mg/kg i.p.) were also significantly potentiated by chronic amphetamine pretreatment. The amino acid precursor of DA, L-tyrosine (25 mg/kg i.p.), and a DA reuptake blocker, bupropion (5 mg/kg i.p.) were without significant effect on these behaviors in amphetamine-treated cats. The data suggest that these cat behaviors are elicited by an action at central DA receptors and that these receptors become supersensitive following chronic amphetamine administration. Furthermore, there may be a qualitative change in DA receptors, since L-DOPA is very effective in potentiating these behaviors in cats treated chronically with amphetamine, but is totally ineffective in naive cats.

Animals↗

PubMed1984

Ontogeny of the behavioral effects of lysergic acid diethylamide in cats.

The ontogeny of the behavioral effects of lysergic acid diethylamide (LSD) was examined in cats between the ages of 4 and 112 days postpartum. The kittens showed little LSD-induced behavioral change prior to 14 days of age. By the age of 21 days, however, the kittens exhibited many of the behavioral signs characteristic of LSD-induced behaviors in adult cats. These behaviors include limb-flicking, abortive grooming, head-shakes, grooming, and investigatory responses. In general, these behaviors began at a low frequency of occurrence, then increased rapidly with advancing age, reaching adult values by approximately 35-40 days of age, and remained relatively constant through 112 days postpartum. The time course for the behavioral effects following an acute injection of LSD showed the adult pattern, i.e., persisting for approximately 8 hr post-injection, from their earliest appearance during ontogeny. Young kittens (21-42 days of age) were resistant to the development of tolerance following repeated administration of the drug. LSD was capable of eliciting certain behaviors, such as head-shakes and grooming, well in advance of the age at which they normally appear spontaneously. This indicates that the neuronal and musculature substrata are developed for the performance of these behaviors long before the kitten naturally employs them.

Aging↗

PubMed1984

Activity of serotonin-containing nucleus centralis superior (Raphe medianus) neurons in freely moving cats.

Presumed serotonin-containing neurons in the nucleus centralis superior (NCS) in freely moving cats showed a slow, rhythmic discharge rate during quiet waking (X = 2.41 +/- 0.12 spikes/s), and displayed a strong positive correlation with level of behavioral arousal. Unit activity during phasic and tonic arousal, as elicited by acoustic stimuli, was increased by 76% and 31%, respectively, and unit activity decreased to active waking levels as the arousal response habituated. During active waking, unit activity was significantly increased by 18% as compared to quiet waking, but there was no correlation between unit activity and phasic body movements. NCS unit activity showed a significant decrease of 15% during drowsiness (first appearance of EEG synchronization) as compared to quiet waking, and then progressive decreases during the early (-27%), middle (-41%) and late (-67%) 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, remain at this low level during the occurrence of the spindle, and then increase immediately after the spindle. NCS unit activity showed decreases of 73% during Pre-REM (the 60 s immediately before REM onset) and 84% during REM, as compared to quiet waking. Unit activity reappeared on the average 2.7 s before the end of REM with significant increases in activity of 60% and 28% during the first second and first 10 s of unit activity, respectively, as compared to quiet waking. NCS neurons showed no significant changes in activity across the 24-h light-dark cycle, when behavioral state was held constant. Seventy-eight % of NCS units were excited by phasic auditory stimulation, with a mean latency of 41 +/- 3 ms and a mean duration of 34 +/- 4 ms. The response to repetitive auditory stimulation showed no evidence of habituation and was even present during sleep. A similar response was evoked by phasic visual stimulation in 68% of the cells tested. A small subset of cells (12%) were inhibited by phasic auditory and visual stimuli. NCS neurons were inhibited by low doses of 5-methoxy-N,N-dimethyltryptamine (50 micrograms/kg, i.m.) or LSD (50 micrograms/kg, i.p.). These data demonstrate that serotonin-containing NCS neurons exhibit properties very similar to those in the nucleus raphe dorsalis, but are different in many respects from medullary serotonergic neurons.

Animals↗

PubMed1984

Effects of diazepam on behavior and dopamine-containing substantia nigra units in freely moving cats.

Administration of diazepam at doses that produced ataxia (5-10 mg/kg IP) significantly decreased the discharge rate of substantia-nigral dopamine-containing neurons by 28.1% in freely moving cats. Diazepam also altered the characteristic decremental bursting pattern of these neurons, producing a steady rhythmic discharge pattern. Similar results were obtained with another centrally acting muscle-relaxant drug, mephenesin. However, the peripherally acting muscle relaxant dantrolene did not produce these effects. These data suggest that diazepam and other centrally acting muscle relaxants may produce their effects on motoric behavior in part by altering the dopaminergic input to the striatum.

Action Potentials↗

PubMed1984

Effects of chronic administration of D-amphetamine on PGO wave activity in the cat.

The effects of depletion of serotonin by the chronic administration of amphetamine (twice daily, 7.5 mg/kg per injection on days 1-6; 15 mg/kg per injection on the remaining days, i.p.) for 10-14 days on ponto-geniculo-occipital (PGO) waves was examined in cats. While the regimen of pretreatment with amphetamine produced comparable decreases in the content of central serotonin (i.e. 40-70%) to those observed in other studies (i.e. with reserpine, p-chlorophenylalanine, methiothepin) of ponto-geniculo-occipital wave activity, no ponto-geniculo-occipital waves of the rapid-eye-movement sleep type were observed during waking after chronic treatment with amphetamine. These results are discussed within the context of the "serotonin gating" hypothesis of the generation of ponto-geniculo-occipital waves, an hypothesis which states that ponto-geniculo-occipital waves emerge into waking when a critical level of the depletion of serotonin is reached, thus opening the "gate" for ponto-geniculo-occipital waves to enter waking states. The present authors suggest that a gradual depletion of serotonin, such as occurs following the chronic administration of amphetamine, will not elicit ponto-geniculo-occipital waves into waking, whereas a rapid depletion of serotonin, such as occurs following treatment with reserpine, results in the emergence of ponto-geniculo-occipital waves into walking.

Animals↗

PubMed1984

Electrophysiological properties of mouse dopamine neurons: in vivo and in vitro studies.

The present experiments were conducted to determine the electrophysiological and pharmacological properties of substantia nigra neurons in the mouse. These cells were studied using extracellular single unit recording and microiontophoretic techniques in both chloral hydrate anesthetized mice and in vitro mouse slices. In the in vivo preparation the substantia nigra zona compacta neurons had long duration action potentials (greater than 4 ms), fired from 1 to 7 impulses/s, and the cells discharged with either a decremental burst pattern or with a regular pattern. The dopamine agonists apomorphine and d-amphetamine, given systemically, decreased the firing rate of these neurons and the dopamine receptor blocker, haloperidol, reversed these effects. The zona compacta neurons were inhibited by the micro-iontophoretic application of dopamine and gamma-aminobutyric acid, and systemic haloperidol selectively attenuated the effects of dopamine. In vitro recordings from substantia nigra zona compacta and zona reticulata neurons were generally similar to those found in vivo, both in terms of the electrophysiological and pharmacological properties. However, the zona compacta cells fired faster in vitro than in vivo, and the firing pattern in vitro tended to be pacemaker-like, especially when recordings were made in an incubation medium which blocks synaptic transmission (e.g. low Ca2+/high Mg2+). Our data indicate that: (a) in vivo mouse zona compacta neurons exhibit the same electrophysiological and pharmacological properties as rat dopamine-containing neurons; (b) in vitro mouse dopaminergic neurons fire with pacemaker regularity when in a low Ca2+/high Mg2+ environment; and (c) in vitro studies offer an approach to examine the basic properties of dopaminergic neurons exclusive of feedback pathways and other afferent inputs.

Animals↗

PubMed1984

A rapid histological technique for localizing recording sites in single unit electrophysiological studies in vitro.

Recording sites from single unit electrophysiological studies in vitro can be precisely localized by first marking the recording locus either by depositing Fast Green dye (for micropipette studies) or electrolytic lesioning (for metal electrode studies). The slices are then fixed in paraformaldehyde, placed in sucrose and attached to a coverslip by the surface tension of water. The slices are attached to a base brain in a cryostat so that the sections can be cut at the proper angle. The slices are then stained using a Nissl staining protocol. This procedure provides intact sections from small tissue slices with the recording locus clearly demarcated.

Central Nervous System↗

PubMed1984

Dopamine-containing ventral tegmental area neurons in freely moving cats: activity during the sleep-waking cycle and effects of stress.

The activity of dopamine-containing ventral tegmental area (VTA) units was recorded by means of movable 32- and 64-microns-diameter insulated Nichrome wires in freely moving cats. The VTA units displayed a slow, somewhat irregular activity during quiet waking (mean 3.63 +/- 0.41 spikes/s) and showed no significant change in activity during slow-wave sleep or REM sleep. Although VTA unit activity was somewhat higher and more erratic during active waking, there was no relationship between unit discharge and phasic movement. These neurons were inhibited (-87%) by small doses of apomorphine (1.0 mg/kg, i.p.) and excited (+43%) by small doses of haloperidol (0.5 mg/kg, i.p.). The stress of a conditioned emotional reaction (CER) paradigm resulted in a significant increase in the discharge rate of VTA neurons (+39%), compared with the quiet-waking baseline. The CER paradigm increased plasma glucocorticoids by 74%. Neurochemical studies revealed that the CER paradigm resulted in a significant decrease of dopamine in the limbic forebrain (-31%), whereas both homovanillic acid (+47%) and dihydroxyphenylacetic acid (+43%) concentrations were increased. No significant changes in dopamine metabolism were observed in the striatum under the CER situation. These data have implications in relation to the role of stress and dopamine in mediating certain psychiatric disorders.

Animals↗

PubMed1984

Differential effects of hallucinogenic drugs on the activity of serotonin-containing neurons in the nucleus centralis superior and nucleus raphe pallidus in freely moving cats.

Previous studies from our laboratory have demonstrated that there are a number of important dissociations between the effects of hallucinogenic drugs on the activity of serotonin-containing dorsal raphe neurons and behavior in freely moving cats. In the present study, we extended this analysis to serotonergic units in the nucleus centralis superior (NCS) and nucleus raphe pallidus (RPA). Lysergic acid diethylamide (LSD) produced a dose-dependent decrease in NCS unit activity at 10, 50 and 100 micrograms/kg (i.p.) and a dose-dependent increase in certain behaviors (e.g., limb flicking and abortive grooming) and the peak behavioral and unit changes were temporally correlated. By contrast, LSD had little effect on serotonin-containing RPA neurons. 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) also produced a dose-dependent decrease in NCS unit activity at 10, 50 and 250 micrograms/kg (i.m.) and dose-dependent behavioral changes. Similar to our LSD data, 5-MeODMT was found to have no overall significant effect on RPA unit activity, except at the highest dose level. Psilocin produced dose-dependent decreases in NCS unit activity at 25, 100 and 750 micrograms/kg (i.p.), whereas the behavioral changes were not dose-related. Psilocin also had relatively little effect on the activity of RPA neurons. The phenylethylamine hallucinogens, 2,5-dimethoxy-4-methylamphetamine (50, 250 and 1000 micrograms/kg i.p.) (DOM) and mescaline (5000 micrograms/kg i.p.), both produced large behavioral changes, but no overall significant effect on raphe unit activity in either the NCS or RPA. These data suggest that ascending dorsal raphe and NCS neurons may be involved in the process of hallucinogenesis, whereas descending RPA neurons do not appear to be involved in this process.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗