The effects of Ca2+ antagonists and hydralazine on central 5-hydroxytryptamine biochemistry and function in rats and mice.

1. The effects of calcium antagonists on behaviour mediated by 5-hydroxytryptamine (5-HT) have been studied in rats and mice together with an investigation of the effects of these drugs on 5-HT synthesis in rat brain and endogenous 5-HT release from brain slices. 2. Administration of felodipine (35 mg kg-1 i.p.) to rats pretreated with tranylcypromine (20 mg kg-1, i.p.) resulted in the animals displaying the complete 5-HT-mediated behavioural syndrome (including head weaving, reciprocal forepaw treading and hind limb abduction) 75 min later. No evidence was obtained for the rate of 5-HT synthesis in brain regions differing between control and felodipine-treated rats. 3. Pretreatment with felodipine (10 or 35 mg kg-1) enhanced the 5-HT-mediated behavioural syndrome induced by injection of tranylcypromine and L-tryptophan. The rate of 5-HT accumulation in the brain was similar in both groups. Administration of Bay K 8644 (1 mg kg-1, i.p.) did not prevent the enhanced behaviour induced by felodipine (10 mg kg-1). 4. The 5-HT behavioural syndrome induced by injection of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was unaltered by either acute injection of felodipine (35 mg kg-1) or administration of felodipine twice daily for 3 days. 5. Felodipine (10 microM), verapamil (10 microM) and Bay K 8644 (10 microM) did not alter either basal release of endogenous 5-HT from slices prepared from frontal cortex or hind brain, or release following addition of K+ at a concentration of 20 mM, or 35 mM.(ABSTRACT TRUNCATED AT 250 WORDS)