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Biomedical subjects

M J McCann

Publications and source records attributed to M J McCann.

36 records · Page 2Linked to original sources
PubMed1988

Dorsal medullary serotonin and gastric motility: enhancement of effects by thyrotropin-releasing hormone.

The effects of serotonin (5-HT) and thyrotropin-releasing hormone (TRH) on gastric motility patterns were investigated. Microinjection of serotonin (8 pmol in 4 nl) into the dorsal motor nucleus of the vagus produced a small increase in motility and tone, an effect which declined with repeated injections. As demonstrated previously, TRH (1 nmol in 1 microliter) applied to the surface of the dorsal medulla evoked a large increase in gastric motility and tone. After gastric motility returned to baseline following the TRH injection, we found that subsequent 5-HT injections, which previously evoked small changes in motility and tone, now evoked large increases in these indices. TRH augmentation of 5-HT-mediated effects on autonomic nuclei may be a significant feature in the alterations in gastric function that accompany the sleep-waking cycle and stress-related gastric pathology.

Animals↗
PubMed1988

Capsaicin pretreatment attenuates multiple responses to cholecystokinin in rats.

Systemic injection of the peptide hormone cholecystokinin (CCK) is known to inhibit food intake and gastric emptying, and to stimulate neurohypophyseal secretion of oxytocin (OT) in rats. Previous studies also have shown that surgical destruction of afferent fibers in the gastric vagus eliminates the inhibitory effects of CCK on food intake. The present experiments used capsaicin to destroy peripheral sensory fibers in rats, and confirmed the failure of CCK to inhibit food intake. Similarly, capsaicin pretreatment markedly attenuated the stimulatory effect of CCK on OT secretion and the inhibitory effect of CCK on gastric emptying in rats. These and other results suggest that in rats CCK acts on receptors located on afferent fibers in the gastric vagus and stimulates inhibition of gastric emptying predominantly via a vagovagal reflex arc through the brainstem.

Animals↗
PubMed1987

Cholecystokinin and gastric distension activate oxytocinergic cells in rat hypothalamus.

Systemic administration of cholecystokinin octapeptide (CCK-8) prompts an abrupt increase in circulating levels of oxytocin (OXY) but not vasopressin (VP) in rats. The present study determined whether CCK-8 selectively stimulated OXY-secreting neurons in the hypothalamic supraoptic nucleus of pentobarbital-anesthetized male rats. Antidromically identified neurosecretory neurons were categorized into putative OXY- and VP-secreting cells on the basis of their firing patterns and response to peripheral baroreceptor activation. Of 36 OXY-secreting cells studied, 30 demonstrated a 50-200% increase in firing frequency within 2 min of administering CCK-8 by intravenous or intraperitoneal injection, whereas none of the eight VP-secreting neurons studied was activated. In related experiments, 4-10 ml of air were used to inflate an intragastric balloon in rats; 20 of 22 OXY-secreting neurons displayed an abrupt and readily reversible increase in firing frequency, whereas only 2 of 17 VP-secreting cells were activated. Gastric distension similarly elevated plasma OXY levels in unanesthetized rats with indwelling gastric cannulas. Together with previous findings that the effects of CCK-8 on OXY release were attenuated by gastric vagotomy, these observations clearly demonstrate the existence of a sensitive neural link between the stomach and the neurohypophysis in the rat.

Animals↗
PubMed1987

Recovery of chronotropic responsiveness after systemic 6-hydroxydopamine treatment: studies in the pithed rat.

In pithed rats, neurally mediated chronotropic responses to thoracolumbar stimulation were reduced substantially 1 day after animals were treated with the neurotoxin 6-hydroxydopamine (6-HDA), which produced a subtotal destruction of postganglionic sympathetic nerve terminals. However, the chronotropic responses of 6-HDA-treated rats recovered to near normal within 1 week despite 90% depletion of cardiac norepinephrine (NE). This recovery of function appeared to depend upon function in surviving sympathetic nerves, and was associated with increased synthesis and release of NE from those neurons as well as diminished inactivation of NE. The gradual development of post-junctional changes, most notably an increase in the density of myocardial beta adrenergic receptors, resulted in enhanced sensitivity to NE and contributed to cardiac function 3 weeks after 6-HDA treatment. In addition, the adrenal medulla increased its synthesis of catecholamines after 6-HDA treatment and thereby contributed to cardiac function, which was especially evident during prolonged sympathoadrenal stimulation. Some of these same adaptations have been observed when rats are subjected to chronic stress, and thus common mechanisms of neuroplasticity may mediate the sympathoadrenal responses to stress and to subtotal injury.

Adenylyl Cyclases↗
PubMed1986

Oxytocin secretion in response to cholecystokinin and food: differentiation of nausea from satiety.

Administration of cholecystokinin (CCK) to rats caused a dose-dependent increase in plasma levels of the neurohypophyseal hormone oxytocin (OT). The OT secretion was comparable to that found in response to nausea-producing chemical agents that cause learned taste aversions. The effect of CCK on OT secretion was blunted after gastric vagotomy, as was the inhibition of food intake induced by CCK. Food ingestion also led to elevated plasma OT in rats, but CCK and aversive agents caused even greater OT stimulation. Thus, after administration of large doses of CCK, vagally mediated activation of central nausea pathways seems to be predominantly responsible for the subsequent decrease in food intake. Despite their dissimilar affective states, both nausea and satiety may activate a common hypothalamic oxytocinergic pathway that controls the inhibition of ingestion.

Animals↗
PubMed1986

Gastric emptying of glucose loads in rats: effects of insulin-induced hypoglycemia.

Previous work has established that the increased food intake of rats in response to insulin-induced hypoglycemia can be inhibited by the intravenous infusion of fructose, a sugar that cannot cross the blood-brain barrier and nourish cerebral chemoreceptors, and that this effect of fructose is abolished by hepatic vagotomy. The present series of experiments examined the effects of these treatments on gastric emptying of various glucose solutions in rats. Gastric emptying of the administered loads decreased in proportion to increasing concentration of glucose solution but not by enough for caloric delivery to be regulated precisely. Insulin-induced hypoglycemia increased the rate at which the glucose solutions emptied from the stomach. This enhanced emptying was suppressed by infusion of fructose, and that suppression was eliminated by hepatic vagotomy. These and other findings support previous proposals that food intake is controlled in part by satiety signals reflecting the nutrient content of the stomach and in part by satiety signals related to the delivery of utilizable calories to the liver.

Animals↗
PubMed1986

Cocaine treatment outcome: cocaine use following inpatient, outpatient, and no treatment.

Based upon a sample of 83 cocaine users self-selected into one of 3 programs, several conclusions seem possible. There seems to be little difference in Ss populations who choose hospital, outpatient or self-help/no treatment. Current hospital aftercare programs may not be appropriately oriented for cocaine users. It appears the hospital program in this study retained fewer than 30% of the Ss in aftercare. Outpatient treatment for cocaine dependency is a viable form of treatment which Ss will participate in for up to 6 months on a fee for service basis. Only about 20% of the Ss who were referred to self-help groups attended more than one meeting. Preliminary outcome data suggest that outpatient treatment may result in a lower relapse rate to cocaine than hospital or no treatment. However, this conclusion is extremely guarded due to a large number of methodological issues and the short follow-up period. Relapse to cocaine use is higher among Ss who returned to alcohol or marijuana.

Cannabis↗
PubMed1985

Visceral factors in the control of food intake.

Some years ago, we reported that the increased blood intake of hypoglycemic rats was inhibited by the intravenous infusion of fructose, a sugar that cannot cross the blood-brain barrier and nourish cerebral chemoreceptors. More recent experiments therefore have focused on visceral factors in the control of food intake. Three observations have been emphasized in this review. First, we found that gastric emptying was increased during insulin-induced hypoglycemia, and that this effect also was eliminated by administration of fructose. Hepatic vagotomy abolished both this effect of fructose on gastric emptying and its effect on food intake. Second, we found that in rats with severe diabetes, the rate of gastric emptying did decrease in proportion to increasing concentration of an administered glucose load, as it does in intact rats, but calories emptied more rapidly than normal regardless of the concentration of the load. Third, we found that rats with varying degrees of streptozotocin-induced damage to the pancreas ate more food than intact rats did after an overnight fast, and that individual intakes were proportional to the induced glucose intolerance. The increased eating took the form of shorter intermeal intervals, as if the initial postfast meal did not remain satiating for a normal amount of time. These and other findings suggest that food intake is controlled in part by satiety signals apparently related to the delivery of utilizable calories plus insulin to the liver. These signals also seem to affect gastric emptying and thereby might influence other satiety signals related to gastric distention.

Animals↗
PubMed1976

Generalization of behaviour therapy with psychotics.

Generalization of improvement in the behavioural treatment of psychotic patients must be planned in after-care settings, and for durability over time. The transfer of clinical gains is not an automatic by-product of treatment with severely and chronically impaired mental patients. Treatment strategies that facilitate generalization from hospital to community are illustrated in a case study using empirical data. Systematic and specific treatment programmes were co-ordinated between a state hospital ward and a community-based day hospital. Setting step-wise and limited goals is a feature of successful outcomes. Maintaining consistency in reinforcement contingencies from hospital to community settings, using natural reinforcers, pinpointing functional behaviours as therapeutic goals, over-learning, and training natural caregivers are methods that promote generalization.

Activities of Daily Living↗
PubMedDate not supplied

Species-specific effects of bombesin on gastric emptying and neurohypophyseal secretion.

Previous reports have demonstrated that systemic injection of cholecystokinin (CCK) in rats produces dose-related decreases in food intake, increases in neurohypophyseal secretion of oxytocin (OT), and decreases in gastric emptying. The present studies determined whether systemic injection of bombesin (BBS), another peptide that potently reduces food intake in rats, had similar effects on OT secretion and gastric emptying. Although BBS produces a dose-dependent inhibition of food intake, even very high doses did not significantly affect plasma OT levels and only slightly decreased rates of gastric emptying. Consequently, despite their similar inhibitory effects on food intake, BBS does not appear to activate the same network of central nervous system pathways as does CCK in rats. However, parallel studies in monkeys demonstrated that systemic injection of BBS was effective in stimulating neurohypophyseal secretion of vasopressin rather than OT, in a pattern both qualitatively and quantitatively analogous to the effects of CCK in this species. Together with previous findings that BBS more potently inhibits gastric emptying in primates than in rats, these results therefore also suggest the presence of significant species differences in the central mechanisms by which BBS acts to reduce food intake.

Animals↗
PubMedDate not supplied

An intensive outpatient approach for cocaine abuse treatment. The Matrix model.

The Matrix model of outpatient treatment was developed during the 1980s in response to an overwhelming demand for cocaine abuse treatment services. The model was constructed using components based upon empirically supported findings from the substance abuse research field. Over the course of development, data were collected on the treatment model and the model was modified based upon empirical evaluation. A pilot study comparing the Matrix outpatient model with an inpatient hospital treatment program produced preliminary support for the clinical utility of the model. An open trial comparing publicly and privately funded patients demonstrated that patients with fewer resources were more difficult to engage and retain in this model of outpatient treatment. In a controlled trial, a clear positive relationship was documented between duration and amount of treatment involvement in the Matrix model and positive outcome at 1 year. Due to a variety of methodological issues, the study was not able to answer definitively the question of clinical efficacy. In all of these studies, patients treated with the Matrix model demonstrated statistically significant reductions in drug and alcohol use and improvements in psychological indicators. This body of work, along with the public acceptance the model has received in the treatment community, support the usefulness of this intensive outpatient approach for cocaine abuse. Further research is underway to provide additional controlled information on the value of this treatment approach.

Alcoholism↗
PubMedDate not supplied

Neurobehavioral treatment for cocaine dependency.

Relapse prevention techniques have recently been incorporated into some nonpharmacologic models of chemical dependency treatment. The neurobehavioral model of cocaine dependency treatment establishes a clear timetable for recovery from cocaine dependency and focuses on four distinct areas of functioning. Strategies for addressing these areas of functioning include the use of relapse prevention methods and individual therapy procedures, family systems materials, 12-Step involvement, and urine testing. The model constructs a comprehensive framework for facilitating involvement in recovery activities that promote positive behavior change. The relapse prevention group component of the model is described, the use of a systematic relapse analysis procedure is presented, and an outline of plans for evaluating the model is discussed. The development of a comprehensive outpatient treatment model for treating cocaine dependency provides a standardized structure within which other treatment interventions (e.g., medication, acupuncture) could be evaluated.

Behavior Therapy↗
PubMedDate not supplied

Cocaine abuse among methadone maintenance patients: are there effective treatment strategies?

Cocaine abuse among patients in methadone maintenance treatment has substantially increased in the past decade. No standard treatment approaches exist to address this problem. Empirical evidence has been collected on the effectiveness of several categories of techniques for treating this problem, including pharmacotherapies, behavioral methods (contingency management and relapse prevention), and methadone dose adjustment. Data on the effectiveness of these techniques is summarized. In addition, other treatment interventions that may be efficacious for this population, including day treatment and sober-living facilities, are described. Finally, methadone clinic management procedures that may aid in the reduction of cocaine abuse by methadone patients are discussed. Although many of these efforts are in early stages of evaluation, there are some reasons for optimism in the development of treatment for these patients.

Cocaine↗
PubMedDate not supplied

The matrix model of outpatient stimulant abuse treatment: history and description.

The Matrix model was originally developed in response to the cocaine epidemic of the 1980s. The program consists of relapse prevention groups, education groups, social support groups, individual counseling, and urine and breath testing delivered in a structured manner over a 16-week period. The treatment is a directive, nonconfrontational approach which focuses on current issues and behavior change. Several evaluations of the model have supported its usefulness and efficacy with methamphetamine (MA) users. Methamphetamine users appear to respond to treatment similarly to cocaine users and many continue to show improvements at follow-up.

Ambulatory Care↗
PubMedDate not supplied

Moving research into community settings in the CSAT methamphetamine treatment project: the coordinating center perspective.

The CSAT Methamphetamine Treatment Project (MTP) has been established to conduct a ground-breaking exercise in bringing research into a closer relationship with community-based treatment service organizations. In this article, some of the opportunities and challenges faced by the MTP coordinating center as it has attempted to bring research into community treatment organizations are described. Initially, there has been an active, energetic effort to design the study protocol, focus the activities of the project, and prioritize the tasks to be accomplished. The methods for training the research staff and monitoring the conduct of the research in the community sites are described. A number of observations have been made about the different "cultures and values" of the researchers and the seven clinical organizations where the project has been conducted. The myriad mistakes made and lessons learned about how to conduct a rigorous randomized clinical trial in community treatment organizations may be important for future research-treatment efforts. There has been a wealth of experience gained in the first year of this project that may be of use as efforts move forward to reduce the gap between research and practice.

Central Nervous System Depressants↗
PubMedDate not supplied

Addiction pharmacotherapy 2000: new options, new challenges.

There are many indicators that substance abuse research and treatment are going to become better integrated. Hopefully, this development will produce new treatment options and will improve access and effectiveness of care. Among the most significant factors in this period of change are the advances in addiction pharmacotherapy. For the treatment of alcoholism, disulfiram has been joined by naltrexone, and soon acamprosate will be added to the list of available pharmacotherapies. Individuals with opiate dependence who, for 25 years, were limited to a single medication (methadone) now have LAAM as an available treatment. Furthermore, there is eager anticipation that buprenorphine/naloxone will bring many more opiate users into treatment since it appears that this medication will be available to doctors outside the traditional narcotics treatment program settings. Other opiate addiction treatment options, including sustained-release naltrexone and lofexidine, are in active development. The greatest area of challenge for pharmacotherapy research is the search for stimulant addiction medications. NIDA has extensive efforts underway to discover/develop medicines that can help in the treatment of cocaine and methamphetamine users. During the next decade, those who embrace these new treatments and integrate them into standard care will offer their patients the best chance for recovery.

Acamprosate↗