Quantitative EEG in the prediction of antidepressant response to imipramine.

The purpose of this study was to examine the utility of quantitative electroencephalography (QEEG) in the prediction of response to imipramine in depressed patients. Forty patients with a diagnosis of unipolar depression were subjected to a placebo washout and were assessed at pre-drug, 3 h after their first dose of imipramine, and again 2 weeks into treatment. Following 4 weeks of open imipramine treatment, patients were separated into responder (R) and non-responder (NR) groups. Statistical analysis of the 29 patients who completed the study focused on group comparisons of power spectral estimates in four frequency bands from multi-channel recordings. Results showed that theta power differentiated R and NR groups prior to treatment, in response to an acute test dose, as well as after 2 weeks of active drug treatment. Results based on this exploratory study suggest that QEEG may be a useful early predictor of response to imipramine.

Psychiatric progress. The learned helplessness model of depression.

Attempts have been made to model certain human psychopathological states in the laboratory, with varying degrees of success. The animal model has emerged as an alternative to clinical studies in psychiatry because it is able to provide greater experimental control and allows the exercise of ethical discretion. Although numerous animal models of depression have been proposed in the literature, most, if not all, fail to mimic human depressive symptomatology; their main function is to act as selective screens for antidepressant drugs. The learned helplessness approach has been suggested as an animal analogue of depression because of its similarities to the human depressive state in terms of provocation, manifestation and treatment. Furthermore, the learned helplessness model, which was originally based on animal experimentation, has been shown to be reproducible in human subjects, a finding not observed with other animal models of depression. Although this model has been much criticized in the past, recent reformulation adds credence to it as a more valid analogue of human depression, given the additional cognitive constructs in depressed human subjects.

Time-dependent changes in plasma prolactin level and stress controllability in rats.

1. Numerous studies have shown the importance of controllability factors in the neurochemical, hormonal and behavioural changes associated with presentation of stress stimuli. 2. Previous work from our laboratory revealed that animals exposed to escapable shock had significantly higher prolactin levels than those treated with inescapable shock. 3. The present experiment examined the time-course of plasma prolactin change as a function of shock controllability. 4. Rats were exposed to intermittent escapable, inescapable or no shock for 5, 10, 30 or 60 min and sacrificed for plasma prolactin determination. Additional groups received 60 min shock condition followed by 30 or 60 min rest period prior to sacrifice. 5. Results showed that subjects exposed to 5, 10 or 30 min of escapable shock exhibited higher prolactin levels than inescapable shock or no-shock treated animals. These findings show that the prolactin response to stress is sensitive to controllability factors and is time-dependent.

Effects of nortriptyline treatment on learned helplessness in the rat.

Using an escape delay procedure previously shown to elicit behavioral deficits in mice exposed to uncontrollable shock, rats treated with inescapable but not escapable shock or no shock displayed comparable interference effects when tested in a two-way shuttle box 24 hr later. Treatment with 12.5 mg/kg nortriptyline for 4 or 6 days counteracted the escape deficits produced by inescapable shock while the 0 or 2 day administration regimens were without any appreciable effect. The finding that interference effects produced by inescapable shock were sensitive to sub-acute but not acute drug administration supports the utility of the learned helplessness model in evaluating potential antidepressant agents in experimental animals.

Effects of low and moderate doses of chlorpromazine on discrimination learning in the rat.

The effects of chlorpromazine on the acquisition of a brightness discrimination with food reward were examined. Doses of 0.5, 1.0 or 2.0 mg/kg of CPZ as well as saline were administered intraperitoneally to 4 groups of 7 Sprague-Dawley rats, 1 h prior to testing. After a 3-week period of habituation and pre-training, rats were tested 20 trials a day, 7 days a week. No drug effect was found on the number of trials to reach a criterion of 18/20 successive correct responses, which required an average of 6.2 days of training. Precriterion latencies, however, showed an increase as a function of increasing dose level. Post-choice latencies were not affected, eliminating motor retardation as an explanation for the latency effect.