Insulin counter-regulatory factors, fibrinogen and C-reactive protein during olanzapine administration: effects of the antidiabetic metformin.

In this study, the Authors assessed some insulin counter-regulatory factors, fibrinogen and C-reactive protein after olanzapine administration, and the effect of metformin on these variables, 37 patients with chronic schizophrenia were given olanzapine (10 mg/day for 14 weeks). Nineteen patients received metformin (850-2550 mg/day) and 18 received placebo in a randomized, double-blind protocol. The following variables were quantified before and after olanzapine: cortisol, leptin, tumor necrosis factor-alpha, glucagon, growth hormone, fibrinogen and C-reactive protein. Results were correlated with the changes in body weight and the insulin resistance index. We have reported elsewhere that metformin did not prevent olanzapine-induced weight gain, and the insulin resistance index significantly decreased after metformin and placebo; Baptista T, et al. Can J Psychiatry 2006; 51: 192-196. Cortisol, tumor necrosis factor-alpha and fibrinogen levels significantly decreased in both groups. Glucagon significantly increased after metformin (P=0.03). Leptin tended to increase after placebo (P=0.1) and displayed a small nonsignificant reduction after metformin. The C-reactive protein did not change significantly in any group. Contrarily to most published studies, olanzapine was associated with decreased insulin resistance. Decrements in cortisol, fibrinogen and tumor necrosis factor-alpha levels point to an improvement in the metabolic profile. The trend for leptin to increase after placebo, but not after metformin in spite of similar weight gain suggests a beneficial effect of this antidiabetic agent.

Noxious stimulation increases glutamate and arginine in the periaqueductal gray matter in rats: a microdialysis study.

The periaqueductal gray matter (PAG) is an important center in the modulation of behavioral responses during nociception and stress. In the present experiment, extracellular excitatory amino acid overflow in the PAG was measured every 30 s during noxious stimulation. A combination of in vivo brain microdialysis in freely moving rats and capillary zone electrophoresis with laser induced-fluorescence detection allowed us to detect short lasting changes of excitatory amino acid in dialysates. A formalin injection in the hindpaw of the rat increased glutamate, arginine and aspartate concentration in PAG dialysates. This increase was calcium and nerve impulse-dependent, suggesting neuronal and glial origin of glutamate and arginine, respectively. Handling, pinching or saline injection in the hind paw did not increase glutamate showing that this neurochemical phenomenon is related to painful and persistent noxious stimulation. The results suggest that a rapid excitation of the PAG occurs during noxious stimulation. The role of glutamate and arginine in analgesia is discussed.