The [14C]2-deoxy-D-glucose method of Sokoloff et al. (Sokoloff, L., M. Reivich, C. Kennedy, M.H. Des Rosiers, C. S. Patlak, K. D. Pettigrew, O. Sakurada, and M. Shinohara (1977) J. Neurochem. 28:897-916) weas used to study local cerebral glucose utilization (LCGU) in rats treated with gamma-aminobutyric acid (GABA) agonist (muscimol and 4,5,6,7-tetrahydroisoxazolo[5,4-C]pyridin-3-ol, THIP) and antagonist (bicuculline) drugs. It was of interest to determine if the pattern of LCGU responses to GABA agonists and antagonists administered systemically in vivo would reflect the known distributions of markers for central GABAergic synapses. The patterns of LCGU responses to muscimol and THIP generally were similar. Most brain regions showed dose-dependent decreases in LCGU; others showed no effects; but the red nucleus showed an increase. The GABA antagonist bicuculline produced convulsions and variable LCGU responses, depending on the time of administration. Bicuculline also partially antagonized the depressant effects of muscimol of LCGU. The magnitudes and distribution of in vivo cerebral metabolic responses to specific GABA agonists were not correlated simply with markers for GABAergic synapses. This lack of correlation indicates that additional factors, such as neural circuitry, regulate the LCGU responses to GABAergic drugs.

The efficacy resulting from adjunctive use of supraphysiological doses of levothyroxine has emerged as a promising approach to therapy and prophylaxis for refractory mood disorders. Most patients with mood disorders who receive treatment with supraphysiological doses of levothyroxine have normal peripheral thyroid hormone levels, and also respond differently to the hormone and tolerate it better than healthy individuals and patients with primary thyroid diseases. Progress in molecular and functional brain imaging techniques has provided a new understanding of these phenomena, illuminating the relationship between thyroid function, mood modulation and behavior. Thyroid hormones are widely distributed in the brain and have a multitude of effects on the central nervous system. Notably many of the limbic system structures where thyroid hormone receptors are prevalent have been implicated in the pathogenesis of mood disorders. The influence of the thyroid system on neurotransmitters (particularly serotonin and norepinephrine), which putatively play a major role in the regulation of mood and behavior, may contribute to the mechanisms of mood modulation. Recent functional brain imaging studies using positron emission tomography (PET) with [ (18)F]-fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine affects regional brain metabolism in patients with hypothyroidism and bipolar disorder. Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research.

The [14C]2-deoxy-D-glucose technique (Sokoloff, L., M. Reivich, C. Kennedy, M. Des Rosiers, C. Patlak, K. Pettigrew, 0. Sakurada, and M. Shinohara (1977) J. Neurochem. 28: 897-916) was used to examine the effects of central muscarinic stimulation on local cerebral glucose utilization (LCGU) in the cerebral cortex of the unanesthetized rat. Systemic administration of the muscarinic agonist oxotremorine (0X0, 0.1 to 1.0 mg/kg, i.p.) increased LCGU in the neocortex, mesocortex, and paleocortex. In the neocortex, OX0 was more potent in elevating LCGU of the auditory, frontal, and sensorimotor regions compared with the visual cortex. Within these neocortical regions, OX0 effects were greatest in cortical layers IV and V. OX0 effects were more dramatic in the neocortex than in the meso-or paleocortex, and no significant effect occurred in the perirhinal and pyriform cortices. 0X0-induced LCGU increases were not influenced by methylatropine (1 mg/kg, s.c.) but were antagonized completely by scopolamine (2.5 mg/kg, i.p.). Scopolamine reduced LCGU in layer IV of the auditory cortex and in the retrosplenial cortex. The distribution and magnitude of the cortical LCGU response to OX0 apparently were related to the distributions of cholinergic neurochemical markers, especially high affinity muscarinic binding sites.

Aging is associated with a loss of cyclic gonadotropin release in female animals. This deficit may reflect dampened circadian rhythmicity of neuroendocrine events and/or altered function in hypothalamic nuclei important to regulation of cyclic female reproduction. The purpose of this study was to determine if diurnal periodicity and glucose metabolism in the hypothalamus are altered with age and whether such changes could help to explain the age-related deficits in gonadotropin release. Young (3-4-month-old) and old (18-21-month-old) rats were ovariectomized and subjected to the 2-deoxy-D-1-14C-glucose technique to measure rates of cerebral glucose utilization (GU), an index of neural function (Sokoloff et al., 1977) in various brain areas and in the pineal gland. We measured GU during the light (1400 hours) and the dark (2200 hours) in 17 anatomical regions including the following hypothalamic areas: medial preoptic nucleus, suprachiasmatic preoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus, arcuate nucleus, and median eminence. Serum concentrations of luteinizing hormone (LH) and prolactin were measured in the same rats to determine the effect of age on both of these hormones. Diurnal periodicity of GU was observed in the suprachiasmatic nucleus and the pineal gland in young and old rats. Although there was no age difference in GU of the pineal gland, GU was reduced during the light and dark in the suprachiasmatic nucleus and all other hypothalamic areas examined except the suprachiasmatic preoptic nucleus and the median eminence. Ovariectomy induced an attenuated increase in concentrations of LH in old, compared to young rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The 2-deoxy-D[1-14C]glucose method of Sokoloff was used to measure local cerebral glucose utilization (LCGU) in rats after injections of the GABA receptor agonist, muscimol (1.6 mg/kg and 4.0 mg/kg, i.v.); the muscarinic receptor antagonist, scopolamine (0.4 mg/kg and 2.0 mg/kg, i.v.); or combinations of both drugs. The aim was to identify brain regions where functional effects of GABAergic-cholinergic interactions could be seen. As noted previously, muscimol reduced LCGU in many brain regions. In contrast, scopolamine alone had no effect on LCGU in most brain regions; however, decreases were seen in the medial geniculate body, medial thalamic nucleus, and auditory and frontal cortical areas. Scopolamine increased LCGU in the cerebellar vermis and mesencephalic reticular formation. Although muscimol alone did not significantly affect LCGU in the external plexiform layer of the olfactory bulb or the anterior, periventricular, and parafascicular thalamic nuclei, rats treated with 0.4 mg/kg of scopolamine before 4.0 mg/kg of muscimol had LCGU decrements in those brain regions. Furthermore, the muscimol-induced decrease in LCGU in the medial cortex was enhanced by prior treatment with 0.4 mg/kg of scopolamine. In contrast, in certain brain regions where muscimol alone reduced LCGU (locus ceruleus; central gray matter; striatum; ventral, medial, reunients , and rhomboid thalamic nuclei; and the auditory cortex), scopolamine pretreatment antagonized these decrements. These findings suggest that endogenous cholinergic and GABAergic systems act antagonistically in some brain regions. However, in other brain regions, cholinergic transmission is required for full expression of GABAmimetic effects on LCGU.(ABSTRACT TRUNCATED AT 250 WORDS)