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Biomedical subjects

J Zohar

Publications and source records attributed to J Zohar.

At least 55 records · Page 3Linked to original sources
PubMed1993

Clomipramine treatment of obsessive compulsive symptomatology in schizophrenic patients.

BACKGROUND: Schizophrenic patients with obsessive compulsive symptoms have poor prognoses. Clomipramine is an effective antiobsessional agent, but its possible antiobsessional effect in schizophrenic patients with obsessive compulsive symptoms who are taking neuroleptics has not been studied. METHOD: We conducted an open pilot study in which we added clomipramine to ongoing neuroleptic regimens of five chronic DSM-III-R schizophrenic (N = 3) or schizoaffective (N = 2) patients who were consecutively admitted for treatment during an active phase. Clomipramine treatment was subsequently discontinued in two patients (off-on-off design), whereas it was discontinued and then reinstituted in three patients (off-on-off-on design). RESULTS: All five patients had substantial reductions in previously persistent obsessive compulsive symptoms, and all experienced relapse of their obsessive compulsive symptoms after clomipramine treatment cessation. In the three patients for whom the authors were able to reinstitute clomipramine, an improvement in obsessive compulsive symptoms was noticed once again. Only one patient had an exacerbation of her psychosis with the combined treatment. CONCLUSION: The addition of clomipramine, a serotonin reuptake blocker, to ongoing neuroleptic treatment in schizophrenic patients with obsessive compulsive symptoms was associated with specific reductions of those symptoms. Further studies of antiobsessional agents in selected schizophrenic patients appear warranted.

Adolescent↗
PubMed1992

Sleep deprivation in rapid-cycling bipolar affective disorder: case report.

We describe a 4-month long hypomanic response to sleep deprivation in a patient with consistent (20-day cycles) rapid cycling. He subsequently reverted to very rapid cycling; however, sleep deprivation remained effective for each attack of depression. Sleep deprivation treatment, its immediate but short-lived beneficial effect, may have a role in the treatment of the ultra-short depressions encountered in very rapid cycling.

Bipolar Disorder↗
PubMed1992

Current concepts in the pharmacological treatment of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and often disabling disease. OCD is characterised by intrusive, unwanted and persistently recurring mental events (obsessions) that usually evoke discomfort or anxiety, and/or repetitive ritualistic behaviours (compulsions) that are aimed at reducing discomfort and anxiety. However, the compulsions succeed only in achieving transient relief, followed by a growing sense of pressure. 10 years ago, OCD was considered a rare and treatment-refractory disorder. Recent well designed studies document a lifetime prevalence rate for OCD of more than 2% in the general population. The outlook for patients with OCD has changed in the last decade, with many well controlled studies showing that OCD patients respond to specific behavioural and pharmacological treatments. The specific form of behavioural therapy is in vivo exposure coupled with response prevention. Only serotonin reuptake inhibitors, such as clomipramine, fluoxetine and fluvoxamine, are effective in the treatment of both depressed and not depressed OCD patients. Fluoxetine and fluvoxamine lack the anticholinergic side effects of clomipramine and, thus, provide an alternative treatment for patients who cannot tolerate clomipramine. Other nonserotonergic antidepressants (tricyclics and monoamine oxidase inhibitors) and anxiolytic agents have not been found to be consistently effective in this disorder. Insufficient data on the efficacy of neuroleptics and their potentially irreversible side effects limit their use in OCD patients. Behavioural and the pharmacological treatment are complementary, and a combination of the 2 therapies is apparently more effective than either modality alone.

Clomipramine↗
PubMed1991

Anxiogenic effects of m-CPP in patients with panic disorder: comparison to caffeine's anxiogenic effects.

The behavioral and neuroendocrine effects of meta-chlorophenylpiperazine (m-CPP), a serotonergic agonist, were compared with the effects of caffeine, an adenosine antagonist, in panic disorder patients. Patients with panic disorder were given single oral doses of 0.5 mg/kg m-CPP, 480 mg caffeine, and placebo on separate days under double-blind conditions. Both m-CPP and caffeine had significantly greater anxiogenic and panic-inducing effects than placebo, although caffeine produced nonsignificantly greater increases on all anxiety rating scales than m-CPP. Both m-CPP and caffeine produced significant equivalent increases in plasma cortisol concentrations, but only m-CPP produced plasma prolactin increases. These findings provide further evidence implicating both the serotonergic and adenosinergic receptor systems in the neurobiology of panic disorder.

Adult↗
PubMed1991

Metergoline blocks the behavioral and neuroendocrine effects of orally administered m-chlorophenylpiperazine in patients with obsessive-compulsive disorder.

The pharmacological probe, meta-chlorophenylpiperazine (m-CPP), administered orally to patients with obsessive-compulsive disorder (OCD) has been shown to induce an acute exacerbation in OCD symptoms as well as an exaggerated anxiogenic response in comparison with controls. The mechanism of m-CPP's behavioral effects in humans remains controversial. To further study m-CPP's actions in OCD patients, we completed a series of double-blind pharmacological challenges in 12 OCD patients. Six OCD patients received four separate challenges: placebo, metergoline, m-CPP, and metergoline plus m-CPP; the second group (n = 6) received metergoline and metergoline plus m-CPP in separate challenges. OCD patients receiving placebo or metergoline alone failed to show evidence of significant changes on any of the behavioral rating scales, in contrast to the patients who received m-CPP alone who exhibited significant increases in anxiety and OCD symptoms. However, the 12 OCD patients who received pretreatment with metergoline before m-CPP experienced no significant changes from baseline OCD symptoms or other behavioral changes. m-CPP's ability to elicit elevations in plasma prolactin was blocked by metergoline pretreatment. Metergoline's ability to block m-CPP's effects on behavior and plasma prolactin lends further support to a serotonergic mediation of m-CPP's effects, including its elicitation of OCD symptoms.

Administration, Oral↗
PubMed1991

Differential effects of antidepressant treatments on fenfluramine-induced increases in plasma prolactin and corticosterone in rats.

Intravenous administration of 5-HT releasing agent, fenfluramine, to rats produced increases in plasma prolactin and corticosterone concentrations. Short-term or long-term treatment with either clorgyline or imipramine did not affect baseline levels of prolactin or corticosterone. On the other hand, short-term but not long-term lithium treatment significantly increased baseline levels of corticosterone but not of prolactin. Short-term treatment with lithium but not clorgyline or imipramine potentiated fenfluramine-induced increases in plasma prolactin but not corticosterone. On the other hand, long-term treatment with clorgyline but not imipramine or lithium attenuated fenfluramine's effect on plasma prolactin but not on corticosterone. These findings demonstrate differential effects of antidepressant treatments on fenfluramine-induced increases in plasma prolactin and corticosterone in rats and are consistent with several other clinical and animal studies demonstrating dissimilar actions of different antidepressant treatments on two different 5-HT-mediated neuroendocrine functions.

Animals↗
PubMed1989

Clomipramine in obsessive-compulsive disorder. Further evidence for a serotonergic mechanism of action.

Data from several previous studies link clomipramine's potent serotonergic effects to its clinical efficacy in reducing the symptoms of obsessive-compulsive disorder (OCD). To investigate this relationship further, we administered the serotonin (5-HT) receptor antagonist, metergoline, and placebo to ten patients with OCD in a crossover study carried out under double-blind, random-assignment conditions. In a previous study of untreated patients with OCD, we found no differences in the behavioral response to single-dose administration of metergoline or placebo. In the present study, patients with OCD receiving clomipramine hydrochloride on a long-term basis (with an average 40% lessening in OC symptoms) responded to a four-day period of administration of metergoline with significantly greater self- and observer-rated anxiety compared with the four-day placebo period. Obsessive-compulsive symptoms also tended to be greater during the metergoline phase, with significant drug-time interactions for both OC symptoms and anxiety peaking on day 4 of the metergoline phase. As anticipated, metergoline lowered plasma prolactin concentrations (providing evidence of physiologically significant 5-HT antagonism) but did not alter plasma clomipramine concentrations. These data further support the hypothesis that clomipramine's therapeutic behavioral effects in OCD are mediated via serotonergic mechanisms.

Adult↗
PubMed1989

Anxiety and cerebral blood flow during behavioral challenge. Dissociation of central from peripheral and subjective measures.

To investigate the relationship between anxiety and regional cerebral blood flow, we administered behavioral challenges to 10 patients with obsessive-compulsive disorder while measuring regional cerebral blood flow with the xenon 133 inhalation technique. Each patient was studied under three conditions: relaxation, imaginal flooding, and in vivo (actual) exposure to the phobic stimulus. Subjective anxiety, obsessive-compulsive ratings, and autonomic measures (heart rate, blood pressure) increased significantly, but respiratory rate and PCO2 did not change across the three conditions. Regional cerebral blood flow increased slightly (in the temporal region) during imaginal flooding, but decreased markedly in several cortical regions during in vivo exposure, when anxiety was highest by subjective and peripheral autonomic measures. These results demonstrate that intense anxiety can be associated with decreased rather than increased cortical perfusion and that ostensibly related states of anxiety (eg, anticipatory and obsessional anxiety) may be associated with opposite effects on regional cerebral blood flow.

Adult↗
PubMed1989

Long-term lithium treatment in rats attenuates m-chlorophenylpiperazine-induced decreases in food intake but not locomotor activity.

Administration of various doses of m-chlorophenylpiperazine (m-CPP, a 5-HT agonist) to rats produced dose-related decreases in food intake and locomotor activity. Long-term (21-25 days) but not short-term (3-7 days) lithium treatment attenuated m-CPP-induced decreases in food intake. However, neither short-term nor long-term lithium treatment had any significant effect on m-CPP-induced decreases in locomotor activity. These findings suggest development of functional subsensitivity of 5-HT1B receptors mediating decreases in food intake and provide further evidence that m-CPP's effects on food intake are mediated by different mechanisms from those regulating locomotor activity.

Animals↗
PubMed1989

Long-term imipramine treatment potentiates m-chlorophenylpiperazine-induced changes in prolactin but not corticosterone or growth hormone levels in rats.

Intravenous administration of m-chlorophenylpiperazine (m-CPP, a selective 5-HT agonist) to rats produced increases in plasma prolactin and corticosterone and a decrease in plasma growth hormone concentrations. Long-term but not short-term imipramine treatment potentiated m-CPP's effect on plasma prolactin, but not its effects on corticosterone or growth hormone. Short-term or long-term imipramine treatment did not produce significant changes in baseline levels of prolactin, corticosterone or growth hormone. These findings are compatible with development of functional supersensitivity of 5-HT receptors mediating prolactin release. Lack of potentiation of m-CPP's effects on corticosterone and growth hormone following long-term imipramine treatment suggests either differential regulation of these hormones by serotonergic and possibly other mechanisms, or different 5-HT receptor subtypes mediating the release of these hormones. Alternatively, adaptive changes in other aminergic neurotransmitter mechanisms such as the noradrenergic system may account for the differential effect of long-term imipramine treatment on m-CPP-induced neuroendocrine changes.

Animals↗
PubMed1989

Hyperlocomotion induced by dopamine or cholecystokinin + dopamine in the nucleus accumbens is not modified by chronic lithium treatment.

1. Peptides such as cholecystokinin have been reported to modulate the effects of dopaminergic agonists on locomotion in rats. 2. The present experiments tested the possibility that lithium interacts with dopaminergic function through the same mechanism by which cholecystokinin potentiates dopaminergic function. 3. The results suggest that dietary lithium has no effect on the ability of either dopamine alone, or the combination of dopamine plus cholecystokinin, microinjected directly into the nucleus accumbens, to stimulate hyperlocomotion.

Animals↗
PubMed1989

Obsessive-compulsive disorder as a 5-HT subsystem-related behavioural disorder.

Involvement of the brain serotonin (5-HT) neurotransmitter system in obsessive-compulsive disorder (OCD) was originally suggested on the basis of therapeutic effects found with the semiselective serotonin uptake inhibitor, clomipramine. More recent studies directly comparing clomipramine with non-selective or norepinephrine-selective uptake inhibitors, such as desipramine or nortriptyline, as well as studies with new, more selective serotonin uptake inhibitors, including fluvoxamine and fluoxetine, have supported that hypothesis. Clomipramine's antiobsessional effect has been augmented with the serotonin precursor, L-tryptophan, or with lithium, which has prominent serotonergic effects. Patients whose OCD symptoms improved on clomipramine worsened when the drug was discontinued (regardless of duration of therapy) and improved when clomipramine was reinstituted. OCD symptoms also worsened when metergoline, a 5-HT antagonist, was given to patients who had improved with clomipramine. Metergoline given alone had no effect. Administration of m-chlorophenylpiperazine (m-CPP), a 5-HT receptor agonist, to untreated OCD patients increased their anxiety, depression, and dysphoria, and exacerbated their OC symptoms. After 4 months of clomipramine therapy, m-CPP failed to produce the same behavioural effects, suggesting an alteration of a 5-HT subsystem (possibly downregulation of some 5-HT receptors). The data reviewed suggest an important role for an abnormal brain 5-HT subsystem in patients with OCD.

Brain↗
PubMed1988

Clorgyline treatment differentially affects m-chlorophenylpiperazine-induced neuroendocrine changes.

Intravenous administration of the 5-HT1B agonist, m-chlorophenylpiperazine (m-CPP) to rats produced increases in plasma prolactin (peak effect at 15 min), corticosterone (peak effect at 30 min) and a decrease in plasma growth hormone (peak effect at 15 min) concentrations. Short-term or long-term clorgyline treatment did not affect baseline levels of prolactin, corticosterone or growth hormone. Short-term clorgyline treatment attenuated m-CPP's effect on corticosterone but not on prolactin or growth hormone. On the other hand, long-term clorgyline treatment attenuated m-CPP's effect on prolactin but not on corticosterone or growth hormone. These findings are compatible with development of functional subsensitivity of 5-HT1B receptors mediating prolactin release following long-term clorgyline treatment. Attenuation of m-CPP's effect on corticosterone following short-term clorgyline treatment suggests either early adaptational changes in a 5-HT receptor subtype mediating corticosterone release, or clorgyline-induced increases in other neurotransmitters such as norepinephrine which may be responsible for attenuating m-CPP's effect on corticosterone.

Adrenal Cortex↗
PubMed1988

Food intake, neuroendocrine and temperature effects of 8-OHDPAT in the rat.

Administration of 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT) to rats produced dose-dependent decreases in food intake and hypothermia, increases in plasma prolactin and corticosterone, and a decrease in plasma growth hormone. 8-OHDPAT administration also induced the serotonin behavioral syndrome at all doses. Pretreatment with metergoline did not affect the 8-OHDPAT-induced behavioral syndrome or decrease in food intake but attenuated the prolactin increase and, furthermore, potentiated 8-OHDPAT-induced hypothermia. Pretreatment with ritanserin or naloxone did not modify 8-OHDPAT-induced changes in food intake, temperature or prolactin. Similarly, pretreatment with phenoxybenzamine, propranolol, clonidine, haloperidol and methiothepin also did not attenuate 8-OHDPAT-induced decreases in food intake. Administration of pindolol alone produced hyperthermia, decreased food intake and enhanced prolactin secretion. Pindolol thus appears to act as a partial 5-HT agonist in addition to being an antagonist at central 5-HT receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Serotonergic responsivity in obsessive-compulsive disorder. Effects of chronic clomipramine treatment.

Clomipramine is a potent serotonin reuptake blocker that decreases the symptoms of obsessive-compulsive disorder (OCD). To investigate whether clomipramine treatment in OCD affects brain serotonergic responsiveness, metachlorophenylpiperazine (mCPP), a selective serotonin agonist, and placebo were given under double-blind conditions to nine patients with OCD before and after treatment with clomipramine. Unlike our previous observations of a marked transient increase in obsessional symptoms and anxiety following 0.5 mg/kg of mCPP, readministration of mCPP after four months of treatment with clomipramine did not significantly increase obsessional symptoms and anxiety. Similarly, the hyperthermic effect of mCPP observed before treatment was eliminated after treatment with clomipramine. These findings are consistent with the development of adaptive subsensitivity to the serotonergic agonist mCPP during clomipramine treatment. A similar alteration in the response to endogenous serotonin may mediate clomipramine's antiobsessional effects.

Adult↗