Faculty Bibliography

Six patients with chronic schizophrenia were studied with positron emission tomography (PET) before and after neuroleptic treatment, using fluorine-18-labeled fluorodeoxyglucose. After treatment, the mean whole-slice glucose metabolic rate at the level of the basal ganglia showed a 25% increase. However, patterns of frontal hypometabolism observed with the schizophrenic patients were not altered by medication. Pattern analysis using the fast Fourier transform was applied to a set of 422 images from a mixed group of normal, depressed, and schizophrenic subjects. Reconstruction of the images with low-frequency coefficients was excellent, reducing considerably the number of variables needed to characterize each image. Hierarchical cluster analysis categorized the transformed images according to anatomical level and subject group (patient versus control). The results suggest the utility of this procedure for the classification and characterization of metabolic PET images from psychiatric patients

Studies have previously demonstrated low somatostatin levels in autopsy cortical tissue from Alzheimer's disease (AD) patients and low somatostatin levels in CSF obtained from subjects with dementia. We evaluated levels of this peptide in 21 non-depressed subjects, 10 with AD, 2 with Parkinson's disease (PD), and 9 with other neurological conditions. The AD patients had significantly lower mean CSF somatostatin than the 'other' neurological patients (14.6 +/- 1.5 S.E.M. versus 26.7 +/- 3.2 pg/ml, p less than 0.005). A demented PD subject had a level in the range of the AD group, while the non-demented PD patient had a value above this range. Thus, all 11 patients with AD or PD dementia, analogous disorders, had levels below 21.8 mg/ml, while 7 of the 10 remaining patients had values above 21.8 pg/ml. Age did not explain this finding

The topics discussed in this article are the neural mechanisms of opiate hedonic effects and the role of endogenous opioids in regulating motivational-affective responses of the organism. First, research on the mechanisms of opiate hedonic effects is briefly reviewed; evidence is discussed which suggests the existence of separate neural substrates for the mediation of opiate analgesia, amelioration of aversive emotion, and reward. In the remainder of the article, recent work of our laboratory is summarized which concerns the role of endogenous opioids in regulating feeding and reward elicited by electrical stimulation in the lateral hypothalamus; evidence is presented which indicates that opioid activity associated with the state of food motivation potentiates reward processes. In addition, evidence is discussed which suggests that this opioid activity may concurrently diminish the organism's emotional responsiveness to competing aversive stimuli. The relevance of this area of research to human opiate abuse is discussed.

Synaptosomes from rat cerebral cortex incubated with 3H-S-adenosyl-L-methionine (3H-SAM) displayed an increase in chloroform- extractable tritium when norepinephrine was added to the reaction mixture. The products of this mixture were maximally generated from intact synaptosomes, only partially inhibited by propranolol, and not enhanced by exogenous phospholipids. Thin layer chromatographic analysis of these chloroform extracts in three solvent systems yielded large norepinephrine- stimulated peaks of radioactivity that did not consistently co-chromatograph with authentic methylated phospholipid standards: phosphatidylmonomethylethanolamine (PME), phosphatidyldimethylethanolamine (PDE), and phosphatidylcholine (PC). Further, attempts to identify these peaks of radioactivity using as standards several putative methylated products of varied chemical classes, failed to elucidate likely candidates. It appears that while norepinephrine markedly stimulates the amount of tritium extracted into the chloroform phase, careful and positive structural elucidation of formed products is required before it can be concluded that these are indeed methylated phospholipids

Feeding was induced in rats by electrical stimulation in the lateral hypothalamus. Naloxone (0.2 and 1.0 mg/kg) produced a dose-related elevation of the frequency threshold for stimulation-induced feeding while quarternary naloxone (2.0 and 10.0 mg/kg) had no effect. Since quarternary naloxone does not readily penetrate the blood-brain barrier, we conclude that the opiate receptors at which naloxone exerts its anorectic action are located in the brain rather than in potential peripheral tissues such as gastrointestinal tract, pancreas or adrenal medulla. The threshold-elevating effect of naloxone only became marked after rats had engaged in one or two 5-sec bouts of feeding. The effect continued to increase following each subsequent bout of feeding. Naloxone therefore appears to inhibit feeding by interacting with post-ingestive factors