A high n-6 polyunsaturated fatty acid diet reduces muscarinic M2/M4 receptor binding in the rat brain.

The aim of this study was to examine the influence of different fat diets on muscarinic acetylcholine receptor binding. Nineteen male Sprague-Dawley rats were divided into four groups and fed a diet of either high saturated fat, n-6 polyunsaturated fatty acid (PUFA), n-3 PUFA or low fat (control) for 8 weeks. Using quantitative autoradiography, [(3)H]pirenzepine binding to muscarinic M1/M4 receptors and [(3)H]AF-DX384 binding to M2/M4 receptors were measured throughout the brain in all four groups. The main findings were that compared to the low fat control group, M2/M4 receptor binding was significantly reduced in the dorsolateral, dorsomedial and ventromedial parts of the caudate putamen (61-64%, p < 0.05), anterior cingulate cortex (59%, p < 0.01), dentate gyrus and CA1-3 fields of the hippocampus (32-43%, p < 0.01) of rats on a high n-6 PUFA diet; however, no differences in M1/M4 receptor binding densities between the four groups were observed. These results suggest that a diet high in n-6 PUFA, but not of n-3 PUFAs or saturated fat, may selectively alter M2/M4 receptor-mediated signal transduction in the rat brain.

Carcinogenicity of saccharin in laboratory animals and humans: letter to Dr. Harry Conacher of Health Canada.

We appreciate this opportunity to provide input to the Health Protection Branch's (HPB's) review of the artificial sweetener saccharin. Concerns with regard to the safety of saccharin are of great public health significance and of great interest to the public because saccharin is consumed by tens of millions of people, including children and fetuses. Any evidence of carcinogenesis--and there is ample such evidence--of such a widely used chemical should spur health officials to minimize human exposure to it. It is worth noting that on October 31, 1997, the Board of Scientific Counselors of the National Toxicology Program, a unit of the National Institute of Environmental Health Sciences (NIEHS), voted not to delist saccharin from its Report on Carcinogens.

Decision-making impairments in the context of intact reward sensitivity in schizophrenia.

BACKGROUND: Deficits in motivated behavior and decision-making figure prominently in the behavioral syndrome that characterizes schizophrenia and are difficult both to treat and to understand. One explanation for these deficits is that schizophrenia decreases sensitivity to rewards in the environment. An alternate explanation is that sensitivity to rewards is intact but that poor integration of affective with cognitive information impairs the ability to use this information to guide behavior. METHODS: We tested reward sensitivity with a modified version of an existing signal detection task with asymmetric reinforcement and decision-making with a probabilistic decision-making task in 40 participants with schizophrenia and 26 healthy participants. RESULTS: Results showed normal sensitivity to reward in participants with schizophrenia but differences in choice patterns on the decision-making task. A logistic regression model of the decision-making data showed that participants with schizophrenia differed from healthy participants in the ability to weigh potential outcomes, specifically potential losses, when choosing between competing response options. Deficits in working memory ability accounted for group differences in ability to use potential outcomes during decision-making. CONCLUSIONS: These results suggest that the implicit mechanisms that drive reward-based learning are surprisingly intact in schizophrenia but that poor ability to integrate cognitive and affective information when calculating the value of possible choices might hamper the ability to use such information during explicit decision-making.