Faculty Bibliography

Lateral ventricular injections of the 'nonspecific' opioid antagonist naloxone (100 micrograms) and the kappa-selective opioid antagonist nor-binaltorphimine (50 micrograms) elevated the electrical brain stimulation frequency threshold for eliciting feeding behavior. Mesopontine aqueductal injections of nor-binaltorphimine, on the other hand, lowered the feeding threshold while naloxone still elevated threshold. These findings suggest the existence of forebrain kappa receptors at which endogenous opioid activity results in a facilitation of feeding while kappa receptors in the brainstem seem to mediate an inhibitory effect

beta-Blockers, particularly propranolol, have been shown to be an effective treatment for neuroleptic-induced akathisia (NIA). To examine the relative contribution of beta-1 and beta-2 receptor blockade to the therapeutic effect of propranolol, we studied a beta-1 selective agent (low dose metoprolol) and a beta-2 specific blocker (ICI 118,551). Both agents ameliorated NIA. To further evaluate instruments for quantifying NIA we compared (a) two sets of clinical ratings during the metoprolol study and (b) clinical and electromechanical ratings of NIA during the ICI 118,551 study. The changes in clinical ratings of NIA after metoprolol were similar for most patients; however, the changes in electromechanical and clinical ratings after ICI 118,551 were similar in less than half of the patients studied

Neuroleptic-induced akathisia (NIA) is a relatively common side effect of neuroleptics, in which patients complain of a subjective sense of restlessness usually referable to the legs and have characteristic motor movements. This paper will review: 1) history of spontaneously occurring syndromes of pathologic restlessness and NIA, 2) the clinical significance of NIA, 3) issues concerning the diagnosis and quantification of NIA, 4) treatments of NIA and 5) possible future directions for research in this area. Special attention will be paid to newer treatments for this syndrome, specifically beta-blockers

Selective agonists for mu- and kappa-opioid receptor types were infused, bilaterally, into the intralaminar central lateral nucleus of the rat. Subcataleptic doses of the mu-agonist, DAGO (0.25 and 1.0 microgram), elevated tailshock threshold for eliciting pain vocalization and motor responses. The hyperalgesic effect of U50,488 is not likely to be the result of antagonist action at a mu 2-isoreceptor; the general mu-antagonist, naloxone, and its less lipophilic quaternary analogue, both failed to produce a significant reduction in pain thresholds. Paralleling their effects on pain, DAGO and U50,488 elevated and reduced, respectively, lateral hypothalamic electrical stimulation threshold for positive reinforcement. These results suggest that medial thalamic opioid mechanisms are not exclusively involved in pain modulation but may generally regulate the responsiveness of the organism to motivating stimuli. Moreover, mu- and kappa-receptors may mediate opposite behavioral effects of opioid peptides

Frontal/posterior ratios of cerebral glucose metabolism as determined by positron emission tomography were significantly lower in 13 chronic schizophrenic patients than in eight normal control subjects, as were absolute metabolic rates in both the frontal and posterior regions. The differences were not accounted for by cerebral atrophy

Twelve psychotic patients received a mean dose of 3.3 mg/day of clonidine. In four clonidine was the only treatment and in the remaining eight clonidine was superadded to a neuroleptic regimen after symptomatology was stable. Clonidine caused reduction of scores for both productive psychotic symptoms and anxiety. Negative symptoms were unaffected. These findings are discussed with respect to the small magnitude of the effects, questions as to specificity of the effects and methodologic limitations of this pilot study