Post-weaning rats were housed alone or in groups for a period of 4 or 8 weeks. A portion of the animals received tricyclic antidepressant treatment, desipramine 20 mg/kg/day, during this period. Animals were then tested behaviorally by forced swimming. Isolation was associated with significantly longer durations of immobility during forced swimming. This was blocked by desipramine treatment. Desipramine treatment did not have a significant effect on the swimming durations of group-housed rats. Hindbrain and midbrain levels of catecholamines were subsequently measured and turnover rates estimated by administration of alpha-methyl-p-tyrosine or saline. Isolated rats had increased levels and decreased turnover of catecholamines. The increase in norepinephrine but not dopamine levels was blocked by desipramine, while antidepressant effects on turnover could not be tested with this method. Reduced social stimulation thus appears to be associated with reduced catecholamine release which may result in the accumulation of these transmitters in the central nervous system. Treatment with desipramine appeared essentially to compensate for reduced social stimulation, blocking isolation-induced noradrenergic neurochemical changes, while having few significant effects on control animals. This study may be helpful in furthering our understanding of how the interaction of organisms with their environment influence catecholamine systems and how antidepressants may act to restore function.

Animals↗

PubMed1990

Evidence for reduced and dysregulated turnover of dopamine in schizophrenia.

The dopamine (DA) hypothesis of schizophrenia proposes that schizophrenia is related to dopaminergic hyperactivity. To examine this hypothesis, this article reviews studies that have measured levels of DA and its metabolites in schizophrenic patients. From these studies, the following conclusions about schizophrenia emerge: (1) levels of DA and its metabolites can be highly variable; (2) DA turnover appears to be reduced in a subgroup of schizophrenic patients characterized as more chronic and treatment refractory, compared with normal controls; (3) DA turnover has been correlated positively with acute symptomatology and negatively with signs of chronic illness; and (4) central DA levels appear to be elevated. These conclusions support the author's hypothesis that DA turnover may be both reduced and dysregulated in schizophrenia. It is speculated that reduced turnover is primarily due to a deficiency in DA release and that dysregulation may result from the disruption of feedback mechanisms. Acute psychosis may be associated with a relative increase in the release of DA impinging on supersensitive postsynaptic receptors made so by chronic synaptic depletion of the transmitter.

Brain↗

PubMed1990

A case of bupropion-associated delirium.

The authors report a case of bupropion-associated delirium characterized by disorganized thinking, memory impairment, fear, and agitation but not disorientation, delusions, hallucinations, or other perceptual distortions. Symptom onset appeared to be dose-related, and a sustained therapeutic response was subsequently obtained at a lower dose of bupropion without recurrence of delirium. Abnormal bupropion metabolism and elevated plasma metabolite levels did not account for the adverse reaction, which instead was hypothesized to reflect dopaminergic effects of bupropion.

Antidepressive Agents↗

PubMed1987

A case of psychosis and delirium following withdrawal from triazolam.

A 53-year-old man with a 3-month addiction to approximately 5 mg/day of triazolam experienced psychosis and delirium following relatively abrupt withdrawal from the drug. In contrast to a previous report suggesting that triazolobenzodiazepine withdrawal may not respond to replacement doses of other benzodiazepines, this patient's withdrawal syndrome was effectively treated with lorazepam.

Delirium↗