Microdialysis study of the effects of sedative drugs on extracellular histamine in the striatum of freely moving rats

T Chikai, R Oishi and K Saeki

Department of Pharmacology, Okayama University Medical School, Japan.

The effects of some sedative drugs on the extracellular concentration of histamine (HA) in the striatum of conscious freely moving rats were examined by in vivo microdialysis coupled with high-performance liquid chromatography-fluorometry. The HA output did not significantly change until 4 hr after intraperitoneal saline injection. Pentobarbital (46 mg/kg i.p.) significantly decreased the HA output by 76% at 0.5 to 1 hr after treatment. Muscimol (5 mg/kg i.p.) and diazepam (20 mg/kg i.p.) also significantly decreased the HA output at 0.5 to 1.5 hr after treatment. delta 9-Tetrahydrocannabinol (5 mg/kg i.p.) induced biphasic changes in the HA output, i.e., a significant increase and a significant decrease were observed at 0 to 0.5 hr and 1.5 to 2.5 hr after treatment, respectively. Reserpine (5 mg/kg i.p.) significantly increased the HA output by 47% to 58% at 0 to 2 hr after treatment. The HA output decreased to a level below 10% of the basal value by 4 hr after treatment with (S)-alpha-fluoromethylhistidine (77 mg/kg i.p.). Reserpine slightly restored the HA output (to about 25% of the original basal value). These results, taken together with our previous results, suggest the following: 1) pentobarbital, muscimol and diazepam inhibit HA release; 2) tetrahydrocannabinol initially increases HA release for a short period but markedly decreases the release thereafter; and 3) reserpine increases the extracellular HA concentration probably as a result of inhibition of its elimination.

Volume 266, Issue 3, pp. 1277-1281, 09/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics