naloxone and Cognition-Disorders

The authors seek to extend understanding and treatment of hospitalized schizophrenics presenting with complications of polydipsia and dilutional hyponatremia. Attending physicians may ask the consultation/liaison psychiatrist to see schizophrenics with hyponatremically-induced delirium or other psychiatric syndromes. The referring physician may or may not have identified polydipsia and dilutional hyponatremia and their complications. This article will help the consultation/liaison psychiatrist recognize early evidence of water imbalance, describe evaluation, and provide somatic and behavioral treatment approaches to this life-threatening syndrome.. Over the past ten years, the authors have treated more than 100 patients with the polydipsia-hyponatremia syndrome. The authors discuss their and others' experience with drugs that help and hinder patients suffering from dilutional hyponatremia. They review current key articles from the polydipsia-hyponatremia syndrome literature including articles identified via Medline search 1985-94.. Schizophrenics with the polydipsia-hyponatremia syndrome most commonly present with polydipsia, polyuria, urinary incontinence, cognitive, affective, and behavioral changes, seizures, or coma. Quantitating polydipsia, hyponatremia, and diurnal changes in body weight facilitate therapeutic interventions. Treatment include patient and caregiver education, drug therapies to better treat psychosis and better treat osmotic dysregulation, behavioral interventions to interdict polydipsia, and diurnal weight monitoring.. Once recognized, acute, subacute, and chronic complications of the polydipsia-hyponatremia syndrome are readily treatable. Besides treating the patient, consultation/liaison psychiatrists can teach their medical colleagues about this syndrome. In so doing, they will enhance the quality of their patients' lives and help the internist and surgeon feel more comfortable when working with schizophrenics.

Topics: Angiotensin II; Anti-Inflammatory Agents, Non-Steroidal; Antipsychotic Agents; Carbamazepine; Cognition Disorders; Demeclocycline; Drinking Behavior; Electroconvulsive Therapy; Humans; Hyponatremia; Lithium; Mood Disorders; Naloxone; Phenytoin; Polyuria; Propranolol; Psychiatry; Psychotherapy; Schizophrenia; Sodium Chloride; Syndrome; Water Intoxication; Workforce

Acute doses of buprenorphine can precipitate withdrawal in opioid dependent persons. The likelihood of this withdrawal increases as a function of the level of physical dependence.. To test the acute effects of sublingual buprenorphine/naloxone tablets in volunteers with a higher level of physical dependence. The goal was to identify a dose that would precipitate withdrawal (Phase 1), then determine if withdrawal could be attenuated by splitting this dose (Phase 2).. Residential laboratory study; subjects (N=16) maintained on 100mg per day of methadone. Phase 1: randomized, double blind, triple dummy, within subject study. Conditions were sublingual buprenorphine/naloxone (4/1, 8/2, 16/4, 32mg/8mg), intramuscular naloxone (0.2mg), oral methadone (100mg), or placebo. Medication conditions were randomized, but buprenorphine/naloxone doses were ascending within the randomization. Phase 2: Conditions were methadone, placebo, naloxone, 100% of the buprenorphine/naloxone dose that precipitated withdrawal in Phase 1 (full dose), and 50% of this dose administered twice in a session (split dose). Analyses covaried by trough methadone serum levels.. Six subjects did not complete the study. Of the 10 who completed, 3 tolerated up to 32mg/8mg of buprenorphine/naloxone without evidence of precipitated withdrawal. For the seven completing both phases, split doses generally produced less precipitated withdrawal compared to full doses.. There is considerable between subject variability in sensitivity to buprenorphine's antagonist effects. Low, repeated doses of buprenorphine/naloxone (e.g., 2mg/0.5mg) may be an effective mechanism for safely dosing this medication in persons with higher levels of physical dependence.

Topics: Administration, Sublingual; Adult; Buprenorphine; Cognition Disorders; Double-Blind Method; Drug Combinations; Female; Humans; Male; Methadone; Middle Aged; Naloxone; Neuropsychological Tests; Opioid-Related Disorders; Psychomotor Disorders; Substance Withdrawal Syndrome

Based on its unique pharmacological profile, buprenorphine may produce less impairment in psychomotor and cognitive performance than methadone. However, the few studies that have investigated the performance effects of buprenorphine in opioid-abusing volunteers examined effects of single acute doses rather than effects of repeated dosing and included a very limited range of measures. The present inpatient study evaluated dose-related effects of repeated administration of the buprenorphine/naloxone combination product (8/2, 16/4, 32/8 mg, sublingual tablets) in eight opioid-dependent volunteers on performance of a broad range of tasks, following a period of 7-10 days of dosing at each level, in a double-blind, within-subject, crossover design. The testing battery included measures of psychomotor speed, time perception, conceptual flexibility, focused attention, working memory, long-term/episodic memory, and metamemory. Supporting the hypothesis of limited impairment with buprenorphine, results revealed minimal impairment in performance as buprenorphine/naloxone dose was increased four-fold. The only significant effect of dose was an impairment in episodic/long-term memory (recognition memory) performance at the highest dose (32/8 mg) relative to the two lower doses. Future studies incorporating larger sample sizes and non-drug controls, as well as directly comparing buprenorphine to methadone and LAAM are needed to further test the hypothesis of limited impairment with buprenorphine.

Topics: Adult; Buprenorphine; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Memory Disorders; Naloxone; Narcotic Antagonists; Neuropsychological Tests; Opioid-Related Disorders; Psychomotor Disorders

Electroconvulsive therapy (ECT) is a highly effective treatment for major depression, but is also associated with characteristic cognitive side effects. Several reports document that endogenous opioids and their receptors are activated by electroconvulsive shock (ECS) and that naloxone in doses sufficient to block endogenous opioid receptors may reverse ECS-induced retrograde amnesia. This placebo-controlled, randomized, within-patient study was conducted to examine the potential of naloxone, given in doses sufficient to block opioid receptors (high dose), to ameliorate acute anterograde and retrograde memory impairments following ECT. Compared to placebo and low dose naloxone, high dose naloxone administered immediately before ECT resulted in significant reductions in anterograde amnesia, and better performance on an attention task. Both low and high dose naloxone improved verbal fluency. There were no beneficial effects of high dose naloxone on retrograde amnesia, and an indication that high dose naloxone may have worsened retrograde amnesia for shape stimuli. There were no effects of high dose naloxone on seizure duration, vital signs, and subjective side effects. The study is consistent with prior research in which change in behavioral and physiological measures was produced principally by naloxone doses sufficient to block endogenous opioid receptors and offers evidence of the potential for ameliorating some adverse cognitive effects associated with ECT.

Topics: Adult; Aged; Amnesia, Retrograde; Analysis of Variance; Cognition Disorders; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Orientation; Placebos; Seizures; Treatment Outcome

The opiate antagonist naloxone has been reported to improve memory in animals and to produce partial improvement in Alzheimer's dementia. The usefulness of naloxone for reversing ECT-induced cognitive impairment was tested by comparing the effects of naloxone and placebo on several tests of cognitive performance in 10 patients who underwent bilateral ECT. No significant differences were found between naloxone and placebo. The results suggest that at the doses used, naloxone is not effective in reversing ECT-induced memory deficits.

Topics: Adult; Aged; Amnesia; Cognition Disorders; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Naloxone; Psychological Tests

Topics: Adult; Aged; Amnesia; Cognition Disorders; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Naloxone; Neurocognitive Disorders; Orientation; Psychological Tests

A double-blind study of repeated subcutaneous administrations of 20 mg naloxone was performed in 10 schizophrenic patients as part of a World Health Organization collaborative project. No clinically obvious treatment effects were observed. None of the analyzed psychopathological symptoms, including hallucinations and unusual thought content, showed a distinct improvement during the 4 consecutive days of naloxone treatment. A slight but statistically significant decrease of symptomatology was found shortly after placebo injection on the first 2 days of treatment. This effect was not present following naloxone treatment. These findings are discussed in view of the hypothesis that increased endorphin activity contributes to the symptomatology of schizophrenic syndromes.

Topics: Adult; Cognition Disorders; Female; Hallucinations; Humans; Injections; Male; Middle Aged; Naloxone; Schizophrenia

Individuals with Alzheimer's disease (AD) are in susceptible patient groups in which pain is an important clinical issue that is often underdiagnosed. However, it is unclear whether decreased pain complaints in patients with AD result from elevated pain tolerance or an impaired ability to communicate sensations. Here, we explored if AD-related pathology is present in key regions of the pain pathway and assessed whether nociceptive thresholds to acute noxious stimulation are altered in the double-mutant APPswe × PS1.M146V (TASTPM) transgenic mouse model of AD. TASTPM mice exhibited an age-dependant cognitive deficit at the age of 6 months, but not at 4 months, a deficit that was accompanied by amyloid plaques in the cortex, hippocampus, and thalamus. In the spinal cord, β-amyloid (APP/Aβ) immunoreactivity was observed in dorsal and ventral horn neurons, and the expression of vesicular glutamate transporter 2 (VGLUT2) was significantly reduced, while the expression of the inhibitory peptides enkephalins was increased in TASTPM dorsal horn, consistent with an increased inhibitory tone. TASTPM mice displayed reduced sensitivity to acute noxious heat, which was reversed by naloxone, an opioid antagonist. This study suggests that increased inhibition and decreased excitation in the spinal cord may be responsible for the reduced thermal sensitivity associated with AD-related pathology.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Analgesics, Opioid; Animals; Brain; Carrageenan; Cognition Disorders; Disease Models, Animal; Locomotion; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Naloxone; Narcotic Antagonists; Nerve Tissue Proteins; Pain; Pain Measurement; Presenilin-1; Recognition, Psychology; Sensory Thresholds

Both methadone- and buprenorphine-treated opioid-dependent patients frequently show cognitive deficits in attention, working memory, and verbal memory. However, no study has compared these patient groups with each other during early opioid substitution treatment (OST). Therefore, we investigated attention, working memory, and verbal memory of opioid-dependent patients within six weeks after the introduction of OST in a naturalistic setting and compared to those of healthy controls.. The sample included 16 methadone-, 17 buprenorphine/naloxone-treated patients, and 17 healthy controls matched for sex and age. In both groups buprenorphine was the main opioid of abuse during the recent month. Benzodiazepine codependence, recent use, and comedication were also common in both patient groups. Analysis of variance was used to study the overall group effect in each cognitive test. Pair-wise group comparisons were made, when appropriate. Methadone-treated patients, as a group, had significantly slower simple reaction time (RT) compared to buprenorphine/naloxone-treated patients. In Go/NoGo RT methadone patients were significantly slower than controls. Both patient groups were significantly debilitated compared to controls in working memory and verbal list learning. Only methadone patients were inferior to controls in story recall. In simple RT and delayed story recall buprenorphine/naloxone patients with current benzodiazepine medication (n = 13) were superior to methadone patients with current benzodiazepine medication (n = 13). When methadone patients were divided into two groups according to their mean dose, the patient group with a low dose (mean 40 mg, n = 8) showed significantly faster simple RT than the high dose group (mean 67 mg, n = 8).. Deficits in attention may only be present in methadone-treated early phase OST patients and may be dose-dependent. Working memory deficit is common in both patient groups. Verbal memory deficit may be more pronounced in methadone-treated patients than in buprenorphine/naloxone-treated patients. In sum, to preserve cognitive function in early OST, the use of buprenorphine/naloxone may be more preferable to methadone use of, at least if buprenorphine has been recently abused and when benzodiazepine comedication is used. Longitudinal studies are needed to investigate if the better performance of buprenorphine/naloxone-treated patients is a relatively permanent effect or reflects "only" transient opioid switching effect.

Topics: Adult; Buprenorphine; Cognition; Cognition Disorders; Drug Therapy, Combination; Female; Humans; Male; Methadone; Naloxone; Opioid-Related Disorders; Reaction Time

Uptake of aluminum may disturb the learning and memory of humans or animals. Naloxone (NAL) has been shown to exert beneficial effects on memory deficits.. We investigated the effects of naloxone on aluminum-induced learning and memory impairment in rats.. Aluminum-induced learning and memory impairment model was established by gavage of Aluminum chloride (600 mg/kg) for 3 months. Rats were divided into three groups viz. naloxone-treated rats (NAL 0.8 mg/kg, i.p. daily for 7 days), non-treated model rats and normal controls.. The Morris water maze test was performed to study spatial learning and memory. Long-term potentiation (LTP) of the Schaffer collateral-CA1 synapse was recorded. Aluminum and zinc contents in the hippocampus were assayed with atomic absorption spectrophotometry.. Parameters of the hidden and visible platform trials and data of LTP were analyzed using two-way repeated measures ANOVA.. In the hidden platform trials, escape latencies of the NAL rats were significantly shorter than that of the non-treated rats (P=0.000, 95% confidential interval low bound 14.31, upper bound 22.68). In probe trails, the number of entries in the target area of the NAL rats (6.75+/-1.28 times/min) was more than that of non-treated model rats (4.56+/-2.16 times/min, P=0.004, 95% confidence interval low bound -3.65, upper bound -0.788). The magnitudes of LTP recorded in the CA1 pyramidal neurons of the NAL-treated rats were significantly augmented when compared to the non-treated model rats (P=0.005, 95% confidence interval low bound 0.16, upper bound 0.84).. NAL could facilitate spatial learning and memory and enhance LTP in the CA1 region of the hippocampus in aluminum-induced learning and memory impairment in rats.

Topics: Aluminum; Animals; Cognition Disorders; Female; Long-Term Potentiation; Male; Maze Learning; Naloxone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley

Physiological stress is known to produce analgesia and memory disruption. A large body of evidence favors the nonopiate mediation of stress-induced analgesia. It is suggested that brain histamine mediates nonopiate analgesia and participates in learning and memory in rodents. Histamine is released during stress, although the nature of histaminergic involvement in stress response is not clearly defined. Therefore, we studied the effect of L-histidine and histamine-receptor antagonists on antinociception and impaired retention induced by immobilization stress. In the present study, immobilization stress produced a naloxone-resistant analgesia that was potentiated by L-histidine and antagonized by pretreatment with the histamine receptor antagonists chlorpheniramine and cimetidine. L-histidine attenuated the memory disruption induced by immobilization stress, which was significantly reversed by chlorpheniramine but not by cimetidine. Thus the involvement of the central histaminergic system, through histamine H1- and H2-receptors, may be speculated in analgesia and cognitive deficit induced by immobilization stress.

Topics: Analgesia; Analgesics; Animals; Chlorpheniramine; Cimetidine; Cognition Disorders; Female; Histamine Agents; Histamine H1 Antagonists; Histamine H2 Antagonists; Histamine Release; Histidine; Male; Maze Learning; Memory Disorders; Mice; Naloxone; Narcotic Antagonists; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Stress, Physiological

Stress can exacerbate a number of psychiatric disorders, many of which are associated with prefrontal cortical (PFC) cognitive deficits. Biochemical studies demonstrate that mild stress preferentially increases dopamine turnover in the PFC. Our study examined the effects of acute, mild stress exposure on higher cognitive function in monkeys and the role of dopaminergic mechanisms in the stress response.. The effects of loud (105-dB) noise stress were examined on a spatial working memory task (delayed response) dependent on the PFC, and on a reference memory task with similar motor and motivational demands (visual pattern discrimination) dependent on the inferior temporal cortex. The role of dopamine mechanisms was tested by challenging the stress response with agents that decrease dopamine receptor stimulation.. Exposure to noise stress significantly impaired delayed-response performance. Stress did not impair performance on "0-second" delay control trials and did not alter visual pattern discrimination performance, which is consistent with impaired PFC cognitive function rather than nonspecific changes in performance. Stress-induced deficits in delayed-response performance were ameliorated by pretreatment with drugs that block dopamine receptors (haloperidol, SCH 23390) or reduce stress-induced PFC dopamine turnover in rodents (clonidine, naloxone hydrochloride).. These results indicate that stress impairs PFC cognitive function through a hyperdopaminergic mechanism. Stress may take the PFC "off-line" to allow more habitual responses mediated by posterior cortical and subcortical structures to regulate behavior. This mechanism may have survival value, but may often be maladaptive in human society, contributing to the vulnerability of the PFC in many neuropsychiatric disorders.

Topics: Animals; Benzazepines; Clonidine; Cognition Disorders; Dopamine; Female; Haloperidol; Macaca mulatta; Male; Memory; Naloxone; Noise; Pattern Recognition, Visual; Prefrontal Cortex; Receptors, Dopamine; Stress, Psychological