Faculty Bibliography

There have been several case reports of improvement in tardive dyskinesia (TD) after treatment with calcium-blocking agents. We have conducted prior single-blind (rater-blind) studies of verapamil and diltiazem and found a statistically significant improvement in TD with verapamil, and a small improvement that did not reach statistical improvement after diltiazem treatment. We now report a single-blind (rater-blind) study of a third calcium antagonist, nifedipine, in the treatment of TD. Nifedipine (30-60 mg/day) was administered to eight schizophrenic patients with TD. Mean AIMS scores on items 1-7 decreased from 12.9 +/- 2.0 (SD) at baseline to 10.8 +/- 2.7 after treatment (t = 3.66, p = 0.01). All subjects were able to tolerate the maximal dose of nifedipine without significant side effects. TD is known to be affected by drugs that affect dopamine neurotransmission. Several lines of pre-clinical and clinical evidence suggest interactions between the calcium antagonists and the CNS dopamine system and provide a possible explanation for the effects on TD seen with calcium antagonists

Many laboratories have reported that systemically administered naloxone has little or no effect on lateral hypothalamic self-stimulation (LH ICSS). In the present study, lateral ventricular infusion of beta-endorphin antiserum and a high dose of naloxone (100 micrograms) produced small but significant increases in stimulation frequency threshold for LH ICSS. beta-Endorphin activity, mediated by a non-mu (e.g. delta or epsilon) receptor, may therefore be involved in the reinforcement of self-stimulation behavior. When rats are deprived of food for 24 h, LH ICSS thresholds decline. Under this condition, systemic naloxone elevates the LH ICSS threshold, often returning it to the pre-deprivation level. In the present study, lateral ventricular infusion of dynorphin A(1-13) antiserum similarly reversed the threshold-lowering effect of food deprivation. The effects of systemic naloxone and intraventricular dynorphin A antiserum on LH ICSS, which are specific to food-deprived animals, may be related to previous findings that these two treatments elevate LH stimulation threshold for eliciting feeding behavior. Results of the ICSS and stimulation-induced feeding studies suggest a model for the mediation of incentive stimuli by dynorphin A activity that is afferent to LH 'reward' neurons and positively gated by 'hunger'. An hypothesized role for 'hunger'-gated dynorphin A release in potentiating the hedonic response to alimentary stimuli and drugs of abuse is discussed

Although opioid antagonists block feeding behavior in a variety of animal models, the number and identity of CNS regions in which the inferred endogenous opioid activity mediates feeding have yet to be established. Furthermore, it is not yet clear whether the opioid activity that sustains feeding is a concomitant of the appetitive motivational state or the consummatory response. In an effort to address these issues, an in vivo autoradiographic method was used to visualize CNS regional changes in opioid release during appetitively motivating electrical stimulation in the lateral hypothalamus (ESLH) and during consummatory behavior elicited by such stimulation. Regional decreases in [3H]diprenorphine [(3H]Dpr) binding, suggesting increased release of an endogenous opioid peptide, were observed in the medial prefrontal cortex, medial septum, gustatory cortex, zona incerta, mediodorsal thalamus, and hippocampus of rats receiving ESLH. Decreased binding in the latter 4 structures did not appear when animals were allowed to eat during ESLH, suggesting that the inferred opioid release is associated with appetitive behaviors elicited by ESLH which are suppressed when food is available and consummatory behavior predominates. When animals were allowed to eat during ESLH, [3H]Dpr binding in anterior cingulate cortex decreased substantially, suggesting that feeding behavior specifically triggers opioid release in this region. ESLH and feeding were found to increase [3H]Dpr binding in a number of CNS regions. Alternative explanations for increased binding, including inhibition of tonic opioid release, changes in cerebral blood flow, and opioid receptor up-regulation are discussed

We investigated response bias (defined as the decision rule subjects adopt when uncertain) in two experiments using a variant of Signal Detection Theory (SDT) with the discrimination measure d'L and the bias measure CL, under which it is possible to independently evaluate discrimination and response bias. In the first experiment, manics, depressed subjects, and matched psychiatrically normal controls were tested with a recognition memory task with easier and more difficult components before and after 1 month of appropriate pharmacological treatment. This experiment showed that abnormally conservative bias was characteristic of depression and liberal (yea-saying) bias was found in mania regardless of severity of illness; discrimination deficits were found only when symptoms were severe. After treatment, aspects of discrimination worsened in both hypomanic and depressed nonresponders whereas response bias remained unchanged in these patients. In both groups of responders, improvements in response bias were more dramatic than improvements in discrimination. In the second experiment, psychiatrically normal hypertensives were tested with a Sternberg short-term memory scanning task on and off treatment with the centrally active beta-blocker propranolol. This experiment showed that treatment with propranolol modeled the bias deficit of depression; that is, bias became more conservative. Both sets of results suggest that disorders of decision may be modulated by beta-adrenergic function

In 1984 as part of a New York City study to examine the prevalence of HIV infection in a substance-abusing population and to test the validity of HIV screening kits, 94 patients at the New York VAMC were tested. Results were made available to 50 (35 seronegative, 15 seropositive) patients in January 1986. Psychological and behavioral impact of learning test results was assessed using standardized psychiatric rating scales. A comparison group of 31 nontested subjects were also evaluated. Ratings were done preresults, approximately 1-2 weeks after results, and 8-10 weeks after informing patients of their HIV status. No major stress reactions were observed. Seropositives experienced a higher level of anxiety 1-2 weeks after learning results but anxiety generally diminished; they made significant behavior changes which were maintained. Seronegatives experienced relief and maintained IV drug risk reduction behavior. Anxiety about contracting AIDS increased in nontested subjects as the study progressed