Biomedical subjects

T Crisp

Publications and source records attributed to T Crisp.

50 records · Page 3Linked to original sources

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

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

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

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↗

PubMed1983

Tolerance develops to LSD while the drug is exerting its maximal behavioral effects: implications for the neural bases of tolerance.

Tolerance to a test dose of 50 mg/kg of LSD occurred within 0.5-1.0 h following an initial dose of 10 mg/kg of the drug, using limb flicking and abortive grooming as behavioral indices in the cat. These findings represent an example of very rapidly developing drug tolerance using a behavioral index. These data are discussed within the context of hypotheses concerning the neurochemical bases of tolerance to LSD.

Animals↗

PubMed1983

Mescaline elicits behavioral effects in cats by an action at both serotonin and dopamine receptors.

The characteristic behavioral effects of mescaline in cats were nearly completely blocked by pretreatment with low doses of either a specific serotonin antagonist (methysergide) or a dopamine specific antagonist (haloperidol). These blocking effects were not due to non-specific actions, since methysergide did not block the behavioral effects of apomorphine, and haloperidol did not block the behavioral effects of 5-methoxy-N,N-dimethyltryptamine. Thus, it appears that the behavioral effects of mescaline are dependent upon the simultaneous action of the drug at both serotonin and dopamine receptors.

5-Methoxytryptamine↗

PubMed1983

Dopamine-containing substantia nigra units are unresponsive to changes in plasma glucose levels induced by dietary factors, glucose infusions or insulin administration in freely moving cats.

Dopamine-containing neurons in the pars compacta of the substantia nigra showed no significant change in activity during 48 hours of food deprivation in cats that were maintained on either a high carbohydrate diet or a low carbohydrate-high protein diet. Plasma glucose levels declined significantly during this time period in the high carbohydrate diet group, and increased slightly in the low carbohydrate-high protein diet group. In addition, there was no significant change in the activity of dopaminergic neurons in food deprived cats during feeding behavior, during which glucose levels were restored to normal. Intravenous infusion of glucose in freely moving cats, which elevated plasma glucose levels from 82 to 719 mg/100 ml and midbrain glucose from 4.3 to 12.2 mumoles/g, was also without effect on the activity of dopaminergic neurons. Insulin administration to cats maintained on a diet of standard cat chow and fasted for 18 hours decreased plasma and brain glucose to 32.8 mg/100 ml and 2.1 mumoles/g, respectively, but, again, there was no significant change in nigral unit activity. These data demonstrate that central dopaminergic neurons are unresponsive to fluctuations in brain and plasma glucose, and argue against a role for central dopamine systems in the regulation of feeding behavior and energy metabolism.

Action Potentials↗

PubMed1982

Behavioral and neurochemical effects of apomorphine in the cat.

Administration of apomorphine (2-10 mg/kg i.p.) elicited a number of behaviors, such as limb flicking, abortive grooming, investigatory and hallucinatory-like responses, head and body shakes, and excessive grooming, which we have previously proposed as an animal model for studying the actions of LSD and related hallucinogens. Repeated administration of apomorphine resulted in a significant tolerance, which occurred within 2 h of the initial injection, and completely dissipated within 24 h. A pronounced LSD-apomorphine cross tolerance was observed; however, there was no significant apomorphine-LSD tolerance. Apomorphine-induced behavioral changes were blocked by prior treatment with haloperidol, but were unchanged by pretreatment with L-DOP[A. Administration of L-DOPA, in combination with a peripheral decarboxylase inhibitor, did not elicit these characteristic behavioral changes. Increasing synaptic serotonin levels by monoamine oxidase inhibition, precursor administration, or reuptake blockade in general did not alter the behavioral response to apomorphine. Similarly, pretreatment with serotonin receptor blockers produced no large changes in apomorphine-induced behaviors. Prior serotonin depletion with chronic p-chlorophenylalanine administration, however, potentiated certain apomorphine-induced behaviors. Neurochemical studies revealed that apomorphine administration increased striatal dopamine, and decreased dopamine metabolites. Norepinephrine levels were generally decreased throughout the CNS by apomorphine treatment. Administration of apomorphine increased CNS serotonin and 5-hydroxyindoleacetic acid levels, while tryptophan levels were unchanged. The biological bases of the limb flick model is discussed in the context of these pharmacological and neurochemical studies.

Animals↗

PubMed1982

Behavioral effects of quipazine in the cat.

Administration of quipazine to cats elicits a number of behaviors, such as limb flicking abortive grooming, investigatory behavior and hallucinatory-like behavior, which we have previously proposed as an animal behavioral model for studying the actions of LSD and related hallucinogens. While recent studies have indicated that these model behaviors may not be totally specific for hallucinogenic drugs, the model can still be useful for studying drug action. Quipazine (0.5-5.0 mg/kg i.p.) produced significant increases in limb flicking, abortive grooming, investigatory behavior, hallucinatory-like behavior grooming, head and body shakes, staring and yawning. These behavioral changes persisted for 1-6 h, depending on the dose of quipazine employed. Administration of quipazine (5.0 mg/kg per day) for 5 consecutive days produced no significant tolerance effect on any of these model behaviors. These quipazine induced behavioral changes were potentiated by pretreatment with apomorphine, and partially blocked by pretreatment with haloperidol. Quipazine-induced behavioral changes were potentiated by prior serotonin depletion with p-chlorophenylalanine, and completely blocked by pretreatment with a monoamine oxidase inhibitor or the serotonin precursor, L-5-hydroxytryptophan. These quipazine-induced behavioral changes were also blocked by pretreatment with the serotonin receptor blockers, cinnanserin, methysergide or cyproheptadine. The mechanism of action of quipazine, as well as the neuropharmacology of the limb flick model, is discussed in the content of these studies with serotonergic and dopaminergic drugs.

Animals↗

PubMed1982

Raphe unit activity in freely moving cats: effects of quipazine.

Quipazine 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 10% decrease at 0.5 mg/kg, (i.p.), to a virtually complete depression of activity at 5.0 mg/kg. The effects of quipazine on raphe units occurred with a short latency (5--10 min) and its duration of action was dose-dependent and lasted from 1 to 6 hr. The degree of depression of raphe unit activity was directly related to the frequency of occurrence of a number of behaviors such as limb flicking and abortive grooming. There was a close temporal correlation between the depression of raphe unit activity and the occurrence of these behaviors. These data reveal that quipazine produces behavioral and raphe unit changes similar to those observed after administration of hallucinogens with an indole nucleus.

Action Potentials↗

PubMed1982

Lack of synergism and cross tolerance between tactile stimulus- and LSD-induced limb flicking in the cat.

The hypotheses that LSD-induced limb flicking, as well as tolerance to this behavioral effect following repeated drug administration, are due to alterations in somatosensory thresholds were tested by examining the rate of limb flicking to LSD alone, saline plus water on the limbs, or LSD plus water on the limbs, and by comparing the limb flick rate with water on the limbs in drug tolerant versus non-tolerant conditions. Cats exhibited the same rate of limb flicking in response to water on the limbs regardless of whether they were pretreated with saline of LSD. Furthermore, there was no significant difference in the tactile stimulus-induced rate of limb flicking in the tolerant versus non-tolerant states. These data suggest that LSD-induced limb flicking is not simply a function of drug-induced altered somatosensory thresholds, but is apparently reflective of more complex neural processes.

Animals↗

PubMedDate not supplied

Effects of aging on spinal opioid-induced antinociception.

Initial experiments were conducted to determine whether or not the aging process alters the ability of young, mature, or aged male Fischer 344 rats (5- to 6-, 15- to 16-, and 25- to 26-months-old, respectively) to respond to thermal nociceptive stimuli. Using the tail-flick analgesiometric assay, 25- to 26-month-old rats responded significantly faster to the heat source than 15- to 16-month-old animals, but no significant differences were noted between the 5- to 6-month-old and aged rats. Another series of investigations compared the effects of aging on the spinal antinociceptive properties of the mu opioid agonist [D-Ala2,N-methyl-Phe4,Gly5-ol] enkephalin (DAMPGO) and the delta agonist [D-Pen2,D-Pen5] enkephalin (DPDPE). In these studies, young, mature, and aged rats were injected intrathecally (IT) with different doses of DAMPGO or DPDPE, and opioid-induced antinociception was tested on the tail-flick test. All three age groups responded to IT DAMPGO in a dose-dependent manner but, for the most part, higher spinal doses were required to produce significant elevations in tail-flick latency in the aged cohort of rats. The spinal analgesic effects of DPDPE also declined with advanced age. The aging process apparently alters the pain-inhibitory function of mu and delta opioid receptors in the rat spinal cord.

Aging↗

PubMedDate not supplied

Hunter's syndrome and oral manifestations: a review.

Review of the literature on Hunter's syndrome and oral manifestations in pediatric dental patients including the primary and secondary systemic manifestations are presented. Numerous oral manifestations are presented as well. Based on the cases presented in the reviewed studies, little information is available on oral considerations and treatment of these children. Early restoration of the oral cavity is important prior to treatment of the disease itself.

Bone Marrow Transplantation↗