Central cardiovascular and biochemical effects of baclofen in the conscious rat

Baclofen (beta-D-chlorophenyl-GABA, 1.25-10 mg kg-1 i.p.) elicited dose-dependent increases in blood pressure and heart rate in conscious rats. similar responses were observed after intracisternal or intracerebroventricular injections of baclofen 0.125-1 microgram kg-1. Baclofen i.p. was largely ineffective after spinal transection at C7. Pretreatment with phenoxybenzamine, bethanidine or hexamethonium antagonized the cardiovascular effects of i.p. baclofen. These actions were significantly attenuated after catecholamine depletion and synthesis inhibition by means of alpha-methyl-m-tyrosine and alpha-methyl-p-tyrosine. The responses to baclofen were not affected by bilateral adrenal demedullation but abolished by pentobarbitone anaesthesia. Hence, the cardiovascular effects of baclofen are probably evoked from central nervous structures and mediated via the sympathetic nervous system. In doses corresponding to those used in the circulatory studies i.p. baclofen increaed endogenous concentrations of brain DA and decreased DA utilization but only slightly affected brain NA concentrations and utilization.