Acute and chronic effects of caffeine on brain monoamine levels and endocrine function in the rat

Caffeine was given to rats either acutely (1 injection) or chronically (28 daily injections). Both treatments increased brain levels of tryptophan (Trp), serotonin (5-HT) and 5-hydroxyindoleacetic acid in a dose-related fashion, but the apparent stimulatory actions of acute caffeine on the rates of 5-HT synthesis and turnover appeared to have been reduced by repeated exposure to the drug. Acute caffeine increased the blood levels of nonesterified fatty acids (NEFA), glucose and insulin, and reduced the levels of tyrosine (Tyr). Except for Tyr, chronic caffeine substantially reduced the NEFA and glucose responses in magnitude and duration; moreover, daily caffeine significantly lowered serum insulin levels. Chronically caffeinated rats, however, were able to display positive insulin and glucose responses when challenged with an oral glucose load and epinephrine, s.c., respectively. Those events possibly mediating the acute and chronic effects of caffeine on brain Trp and thus 5-HT levels may include, on the one hand, enhanced insulin secretion and increases in the serum Trp ratio, and, on the other hand, lipolysis and the release of plasma Trp from protein binding.