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C W Callaway

Publications and source records attributed to C W Callaway.

At least 19 recordsLinked to original sources
PubMed1992

Stimulant effects of 3,4-methylenedioxymethamphetamine in the nucleus accumbens of rat.

This study examined the behavioral effects in rats of intracerebral administration of S(+)-3,4-methylenedioxymethamphetamine (S-MDMA) using an automated holeboard and open-field apparatus. Administration of S-MDMA into the nucleus accumbens septi produced locomotor hyperactivity. Although the stimulant effects of S-MDMA administered systemically are antagonized by fluoxetine pretreatment, the activating effects of S-MDMA administered into the nucleus accumbens were not antagonized by fluoxetine. A similar increase in locomotor activity was observed after S-amphetamine administration into the nucleus accumbens. In contrast, the selective 5-HT-releasing drug and S-MDMA congener N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB) produces MDMA-like locomotor hyperactivity when administered systemically but did not alter locomotor activity when injected into the nucleus accumbens. These data indicate that S-MDMA actions in the nucleus accumbens are pharmacologically distinct from the primary effects of systemically administered S-MDMA. Behavioral effects of S-MDMA in the nucleus accumbens may result from the catecholamine-releasing properties that S-MDMA shares with S-amphetamine and not via the 5-HT-releasing properties that it shares with MBDB.

3,4-Methylenedioxyamphetamine↗
PubMed1992

Neuronal firing in the nucleus accumbens is associated with the level of cortical arousal.

Because of evidence that the nucleus accumbens mediates the activating effects of many drugs, this study examined the hypothesis that the firing rates of individual nucleus accumbens neurons are positively correlated with spontaneous changes in behavioral arousal that occur during the sleep-wake cycle. The present report examined the firing patterns of 80 neurons in the nucleus accumbens of unanesthetized, unrestrained rats during various electrographically determined levels of arousal. Synaptic responses to stimulation of hippocampal and pallidal nucleus accumbens afferents indicated that the present sample of neurons was similar to a large population of nucleus accumbens neurons previously recorded in anesthetized rats. Confirming the participation of the nucleus accumbens in behavioral arousal, the firing rates of nucleus accumbens neurons were greatest during wakefulness and rapid eye movement sleep and lowest during non-rapid eye movement sleep. Furthermore, the induction of halothane anesthesia decreased behavioral and electrocorticographic arousal concurrent with a suppression of the spontaneous nucleus accumbens unit discharge. These data support the hypothesis that the firing of nucleus accumbens neurons is closely related to arousal.

Action Potentials↗
PubMed1992

Tolerance and cross-tolerance to the activating effects of 3,4-methylenedioxymethamphetamine and a 5-hydroxytryptamine1B agonist.

Previous studies indicate that 3,4-methylenedioxymethamphetamine (MDMA) produces locomotor hyperactivity in rats by increasing the presynaptic release of serotonin (5-HT). Interactions between MDMA and 5-HT receptor antagonists suggest that the activating effects of MDMA are mediated via 5-HT1-like receptors. In order to assess the contribution of particular 5-HT receptor subtypes to the behavioral effects of MDMA, the present studies examined the development of tolerance and cross-tolerance to the behavioral effects of MDMA and selective 5-HT receptor agonists. In the first study, rats were pretreated with saline, a 5-HT1A receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 1.0 mg/kg), a 5-HT1B receptor agonist [5-methoyx-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole butane dioate (RU24969), 2.5 mg/kg] or a 5-HT1C/5-HT2 receptor agonist (2,5-dimethoxy-4-iodoamphetamine, 1.0 mg/kg) twice daily for 3 days. The behavioral response to S-MDMA (3.0 mg/kg) was assessed 36 hr after the last pretreatment injection. Pretreatment with RU24969 antagonized the activating effects of S-MDMA. In contrast, pretreatment with 2,5-dimethoxy-4-iodoamphetamine did not alter the response to S-MDMA, and pretreatment with 8-hydroxy-2-(di-n-propylamino)tetralin reduced the activity of both control and S-MDMA-treated animals. In the second study, rats were pretreated with saline or RS-MDMA (10 mg/kg), twice daily for 4 days. The behavioral response to saline, S-MDMA (3.0 mg/kg), RU24969 (2.5 mg/kg) or S-amphetamine (1.0 mg/kg) was assessed 36 hr after the last pretreatment injection.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Methylenedioxyamphetamine↗
PubMed1992

Serotonin 5-HT1-like receptors mediate hyperactivity in rats induced by 3,4-methylenedioxymethamphetamine.

This study was designed to evaluate the role of different serotonin (5-HT) receptor subtypes in mediating the effects of 3,4-methylenedioxymethamphetamine (MDMA) on rat exploration of a novel environment. The active enantiomer of MDMA, S-MDMA increases forward locomotion and suppresses investigatory behaviors and local movements. Previous studies indicate that S-MDMA-induced hyperactivity depends upon drug-induced 5-HT release. Propranolol and pindolol, beta-noradrenergic antagonists with affinity for 5-HT1 receptors, antagonized the S-MDMA-induced locomotor hyperactivity. The antagonism by propranolol was stereoselective. In contrast, a beta-noradrenergic antagonist that is a weaker antagonist of 5-HT receptors, betaxolol, was much less effective at blocking the behavioral response to S-MDMA. Among nonselective 5-HT antagonists, methiothepin was effective and methysergide and cyproheptadine were ineffective as antagonists of S-MDMA-induced hypermotility. In other systems, methiothepin has been found to be a good antagonist at 5-HT1B receptors where methysergide and cyproheptadine are ineffective. The 5-HT2 antagonist ritanserin was ineffective in blocking S-MDMA-induced hypermotility. However, ritanserin, methysergide, and cyproheptadine partially reversed the S-MDMA-induced suppression of investigatory responding, suggesting a contribution of 5-HT2 receptor activation to this component of the behavioral response to S-MDMA. This study indicates that S-MDMA produces a characteristic form of locomotor hyperactivity in rats that depends upon activation of 5-HT1-like receptors, possibly of the 5-HT1B subtype.

3,4-Methylenedioxyamphetamine↗
PubMed1991

Distribution of amygdala input to the nucleus accumbens septi: an electrophysiological investigation.

The nucleus accumbens septi (NAS) receives afferent input from the amygdala via the stria terminalis and from the hippocampus via the fimbria. Extracellular recordings from 196 NAS neurons in halothane-anesthetized rats revealed heterogeneous response patterns following stimulation of the amygdala. The observation that 30% of anterior NAS units but only 16% of posterior NAS units were responsive to amygdala stimulation suggested a topographical arrangement of amygdala efferents. Comparing the effects of amygdala and fimbria stimulation revealed that the two afferent pathways converge onto individual NAS neurons, but that the two sites of stimulation can differentially influence other neurons. The present results clarify the topographical distribution of amygdala input to the NAS, confirm that inputs from two limbic structures are integrated within the NAS, and further illustrate the electrophysiological heterogeneity of NAS neurons.

Action Potentials↗
PubMed1991

Amphetamine derivatives induce locomotor hyperactivity by acting as indirect serotonin agonists.

Derivatives of amphetamine are potent releasers of both dopamine (DA) and serotonin (5-HT), but the relative contributions of DA and 5-HT release to the behavioral effects of these drugs have not been established. Previously, S-(+)3,4-methylenedioxymethamphetamine (S-(+)MDMA) was found to produce locomotor hyperactivity in rats which was dependent on 5-HT release. The present study found that MBDB (1.25, 2.5, 5.0 or 10.0 mg/kg), the alpha-ethyl derivative of MDMA that produces little or no direct DA release, also induced locomotor hyperactivity that lasted for greater than 60 min after the 5.0 and 10.0 mg/kg doses. MBDB produced spatial patterns of locomotor hyperactivity and suppression of exploratory activity (holepokes and rearings) very similar to the behavioral syndrome produced by MDMA. MBDB-induced hyperactivity was blocked by pretreatment with the selective 5-HT uptake inhibitor fluoxetine (2.5 or 10 mg/kg), suggesting that MBDB produced behavioral effects via uptake-carrier mediated release of 5-HT. Similarly, fluoxetine pretreatment blocked the locomotor hyperactivity produced by S-(+)3,4-methylenedioxyamphetamine (3.0 mg/kg) or p-chloroamphetamine (2.5 mg/kg), supporting a serotonergic basis for the action of these drugs. Tissue levels of 5-HT and its metabolite 5-HIAA were decreased 40 min after administration of S-(+)MDMA (3.0 mg/kg) or MBDB (5.0 mg/kg), and these decreases were prevented by fluoxetine pretreatment. S-(+)MDMA also produced a fluoxetine-sensitive increase of tissue DA levels, suggesting that 5-HT release may indirectly result in increased DA release, although MBDB did not significantly increase DA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Methylenedioxyamphetamine↗
PubMed1990

Serotonin release contributes to the locomotor stimulant effects of 3,4-methylenedioxymethamphetamine in rats.

Methylenedioxymethamphetamine (MDMA) is a phenylethylamine with novel mood-altering properties in humans. MDMA shares the dopamine-releasing properties of amphetamine but has been found to be a more potent releaser of serotonin (5-HT). The present study undertook to determine the relative roles of dopamine and 5-HT release in MDMA-induced locomotor hyperactivity. S-(+)MDMA produced dose-dependent increases of rat locomotion. Investigatory behaviors such as holepokes and rearings were suppressed by (+)MDMA. Pretreatment with the selective 5-HT uptake inhibitors fluoxetine, sertraline and zimelidine inhibited (+)MDMA-induced locomotor hyperactivity but failed to antagonize the reduction of holepokes and rearings. Because 5-HT uptake inhibitors have been found previously to block the MDMA-induced release of 5-HT in vitro, and because fluoxetine was found to have no effect on (+)amphetamine-induced hyperactivity, the present results suggest that (+) MDMA-induced locomotor hyperactivity is dependent on release of endogenous 5-HT. Additionally, prior depletion of central 5-HT with p-chlorophenylalanine partially antagonized the (+)MDMA-induced hyperactivity, although catecholamine synthesis inhibition with alpha-methyl-p-tyrosine did not block the effects of (+)MDMA. Taken together, these studies suggest that (+)MDMA increases locomotor activity via mechanisms that are dependent on the release of central 5-HT and that are qualitatively different from the mechanism of action of (+)amphetamine.

3,4-Methylenedioxyamphetamine↗
PubMed1989

Reserpine enhances amphetamine stereotypies without increasing amphetamine-induced changes in striatal dialysate dopamine.

Indirect evidence suggests that amphetamine (AMPH) releases dopamine (DA) from an extravesicular, cytoplasmic pool. Disruption of vesicular DA storage by reserpine has been hypothesized to increase the concentration of extravesicular DA available for release by AMPH, which is consistent with the observation that reserpine does not prevent but augments the behavioral response to AMPH. In order to more directly test this hypothesis, the in vivo microdialysis technique was used to concurrently examine the behavioral and striatal dopaminergic response to AMPH (1.25 or 2.5 mg/kg) 24 h following reserpine pretreatment (2.5 mg/kg). Reserpine decreased tissue levels of DA by approximately 90% and reduced baseline dialysate DA concentrations by approximately 80%. Reserpine augmented the behavioural effects of AMPH, particularly increasing the occurrence and intensity of stereotypies. In contrast, reserpine did not alter the amount or duration of AMPH-induced DA release. This observation confirms that DA release by AMPH does not depend on vesicular stores but is inconsistent with the hypothesis that augmentation or behaviour by reserpine results from increased striatal DA release.

Amphetamines↗
PubMed1989

The carbachol-induced enhancement of desynchronized sleep signs is dose dependent and antagonized by centrally administered atropine.

Considerable data show that microinjection of carbachol into the pontine reticular formation produces a desynchronized (D) sleep-like state. The present study examined the hypothesis that this carbachol-induced enhancement of D sleep signs is mediated by muscarinic, cholinergic receptors. This hypothesis was tested by quantifying the dose-dependent effects of centrally administered carbachol on the D sleep-like state and by pretreating the animals with centrally administered atropine. Six dosages of carbachol were microinjected into the pontine reticular formation of conscious cats and polygraphic measures of behavioral state were recorded. The percentage, latency, duration, frequency, and time course of the carbachol-induced D sleep-like state were dose dependent. Centrally administered atropine competitively antagonized the ability of carbachol to induce the D sleep-like state, whereas pontine administration of L-glutamate did not significantly alter D sleep. These data demonstrate that muscarinic, cholinergic receptors within the pontine reticular formation mediate the phenomenon of cholinoceptive D sleep sign enhancement.

Animals↗
PubMed1988

Nutritional assessment of intensive-care unit patients.

The decision about whether to institute aggressive nutritional support, with its attendant expense and potential morbidity, in critically ill patients remains controversial. We studied numerous commonly used variables for assessment of nutrition to identify critically ill patients at increased risk for the development of infection, for becoming ventilator dependent, and for mortality. We enrolled 111 patients in this study on their third day in the intensive-care unit (ICU). No attempt was made to influence nutritional support, nor was adequacy of such support studied. Although several measurements correlated with outcome, the serum albumin correlated with number of ICU days (r = -0.38; P less than 0.001), with the number of days on a ventilator, and with the number of hospital days. It was the only measurement that correlated with the development of both a new infection (P less than 0.05) and ventilator dependency (P = 0.002). Although the use of the serum albumin concentration in this setting has limitations, it is still the best, most commonly used measurement of nutrition available.

Adult↗
PubMed1987

Increased ponto-geniculo-occipital (PGO) wave frequency following central administration of neostigmine.

In all mammals so far investigated the occurrence of ponto-geniculo-occipital (PGO) waves precedes the onset and maintenance of desynchronized (D) sleep. As unitary electrographic events, PGO waves provide an index for quantitative evaluation of physiological D sleep or the D sleep-like state evoked by centrally administered acetylcholinesterase inhibitors. The present study characterized PGO wave frequency and time course following central administration of neostigmine bromide (Neo). The results show that Neo produced a dose-dependent increase in PGO wave frequency and time course when injected into brainstem regions other than areas containing putative PGO wave generating neurons. These results support the concept that PGO waves and D sleep are generated by an anatomically distributed network of cholinoceptive neurons.

Animals↗
PubMed1987

Pontogeniculooccipital waves: spontaneous visual system activity during rapid eye movement sleep.

1. Pontogeniculooccipital (PGO) waves are recorded during rapid eye movement (REM) sleep from the pontine reticular formation, lateral geniculate bodies, and occipital cortex of many species. 2. PGO waves are associated with increased visual system excitability but arise spontaneously and not via stimulation of the primary visual afferents. Both auditory and somatosensory stimuli influence PGO wave activity. 3. Studies using a variety of techniques suggest that the pontine brain stem is the site of PGO wave generation. Immediately prior to the appearance of PGO waves, neurons located in the region of the brachium conjunctivum exhibit bursts of increased firing, while neurons in the dorsal raphe nuclei show a cessation of firing. 4. The administration of pharmacological agents antagonizing noradrenergic or serotonergic neurotransmission increases the occurrence of PGO waves independent of REM sleep. Cholinomimetic administration increases the occurrence of both PGO waves and other components of REM sleep. 5. Regarding function, the PGO wave-generating network has been postulated to inform the visual system about eye movements, to promote brain development, and to facilitate the response to novel environmental stimuli.

Animals↗
PubMed1987

Gastric electromechanical and neurohormonal function in anorexia nervosa.

The gastrointestinal motor function in patients with anorexia nervosa is poorly understood, although it may be relevant to the pathophysiology of the disorder. We have undertaken a multidisciplinary study of 8 patients with anorexia nervosa and 8 age- and sex-matched controls. We have characterized their gastrointestinal and neurohormonal function by measuring (a) gastric electrical activity, (b) antral phasic pressure activity, (c) gastric emptying of solids and liquids, and (d) hormonal and autonomic function. Patients with anorexia nervosa at the time of the initiation of therapy presented with (a) increased episodes of gastric dysrhythmia (mean percentage of dysrhythmic time: 9.75 patients vs. 0.48 controls during fasting, p less than 0.02; 7.21 patients vs. 0.18 controls postcibally, p less than 0.001), (b) impaired antral contractility (mean motility index, 12.8 patients vs. 14.2 controls, p less than 0.002), (c) delayed emptying of solids, (d) decreased postcibal blood levels of norepinephrine and neurotensin (levels of beta-endorphin, insulin, glucagon, gastric inhibitory polypeptide, gastrin, cholecystokinin, and human pancreatic polypeptide were normal), and (e) impaired autonomic function (resting diastolic blood pressure and skin conductance were decreased and the response to the cold pressor test was dampened). Differences between patient and control groups were statistically significant. We conclude that patients with anorexia nervosa present multiple gastrointestinal abnormalities involving control mechanisms as well as target organs.

Adolescent↗
PubMed1987

Marine fish oils: role in prevention of coronary artery disease.

Since the early 1970s, investigators have been interested in the relationship between dietary marine fish oils and plasma lipoproteins. Previous studies have shown that consumption of a diet rich in marine fatty acids results in altered lipid profiles, prolonged bleeding times, reduced platelet aggregation, and decreased blood pressure, but the precise mechanisms of action must be examined further. These findings, however, have led to the conclusion that dietary marine fish oils may be of benefit in the prevention of coronary artery disease. Before specific recommendations can be made about their general use, further studies of their long-term efficacy and toxicity must be conducted.

Animals↗
PubMed1986

Vertical gastroplasty for morbid obesity: clinical experience.

Our objective was to develop an operation for morbid obesity that would be simple, safe, and effective and yet have few long-term adverse physiologic effects. Vertical gastroplasty was chosen. A small proximal gastric pouch was fashioned by stapling vertically beginning 5 cm distal to the cardia along the lesser curvature of the stomach and ending just lateral to the esophagogastric junction along the greater curvature. A 1.1-cm channel through the staple line was left near the lesser curvature of the stomach. No gastric incisions, enterostomies, or anastomoses were necessary. Among 57 patients (with a mean +/- SEM preoperative weight of 136 +/- 4.5 kg) operated on since January 1981, no deaths occurred and no gastric reoperations were done. The hospital stay was short (mean, 9 days). In 32 patients who were followed up for 1 year or longer, the mean percentage of excess weight lost was 39% at 6 months, 43% at 12 months, and 34% at 24 months. Two patients had disruption of the staple line and regained weight by 24 months postoperatively. Channel stenosis occurred within 6 months after operation in seven patients, all of whom were managed successfully with endoscopic dilation. We conclude that vertical gastroplasty is a simple, safe operation for morbid obesity with few adverse sequelae, but the percentage of excess weight lost during a 1- to 4-year follow-up exceeded 50% in only 31% of our patients.

Adolescent↗