Increased alcohol preference and consumption, depressed mood, and impulsive aggression are thought to be linked in part through decreased central serotoninergic (5-HT) activity. In agreement with this postulate, certain agents which increase central serotonergic neurotransmission (5-HT precursors, 5-HT uptake inhibitors, 5-HT receptor antagonists) attenuate ethanol intake, improve memory function in intoxicated patients, and may improve memory functions in patients with Korsakoff's psychosis. Recently, a possible pattern of atypical glucose metabolism has emerged in alcohol abusing, impulsive violent offenders with apparent central serotonergic dysfunction. In a group of impulsive offenders, hypoglycemia was possibly due to increased insulin secretion. It is possible that a relative hypoglycemic state or abnormal insulin levels may contribute to violent, aggressive behavior in violent offenders with apparently reduced central 5-HT activity; however, this hypothesis awaits substantially more scientific verification. Although appropriate animal studies have not been performed which demonstrate a cause and effect relationship between altered central serotonin activity and abnormal glucose metabolism, there is overwhelming evidence that appropriate glucose levels are maintained through a complex feedback system which involves the sympathoadrenalmedullary system through the glucose mobilizing hormone epinephrine and the endocrine pancreas via insulin and glucagon secretion. Finally, we have established that serotonergic neurotransmission, particularly events which are mediated via the central 5-HT1A receptor subtype, is a significant mediator of normal glucose homeostasis. Activation of central 5-HT1A receptors increases circulating levels of insulin,glucagon and glucose through a physiological mechanism that requires permissive levels of glucocorticoids and a hormone signal of unknown origin that is released from the anterior pituitary gland. Additional experimental research was not performed during the current fiscal year on this project; however, data analysis and manuscript preparation was carried out.
