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 (35mg kg-i.p.) to rats pretreated with tranylcypromine (20mg 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 35mg 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 (lOmgkg-'). 4 The 5-HT behavioural syndrome induced by injection of the 5-HTlA 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. 7 Hydralazine (5mg kg 1, i.p.) induced the 5-HT behavioural syndrome in tranylcypromine pretreated rats, enhanced the tranylcypromine/L-tryptophan behavioural syndrome, inhibited 5-MeODMT-induced head twitch behaviour in mice and was not a 5-HT2 receptor antagonist. 8 These data indicate that at a high dose, Ca2+ antagonists produce complex changes in 5-HT function in rodents which are similar to those produced by lithium administration. The data with hydralazine suggest that the effects seen are not related to an action at Ca2 + channels. IntroductionRecently Boullin & Grahame-Smith (1987) In both tests the behavioural changes (head weaving, forepaw treading and flat body posture) were measured on a 0-3 score (0: absent, 1: just present; 2: present; 3: severe) as described previously (Deakin & Green, 1978;Goodwin & Green, 1985 Ltd, 1990 42 A.R. GREEN et al.However, in other experiments results are given as the combined behavioural score 40, 60 and 80min after injection and the total score of all 3 observation times. This 'shortened' observation scoring nevertheless reflected the overall pattern of behavioural change.5-HT2 receptor-mediated responses were examined following agonist administration to mice by measurement of the resultant head-twitch response as described in detail previously (Goodwin & Green, 1985). Briefly, mice were injected with 5-MeODMT (5mgkg-1, i.p.) and the total number of head twitches counted in the next 5min. Because of some variability in the response from day to day, control (vehicle injected) animals were always examined with the experimental group and to simplify presentation, results are given as the percentage inhibition of the experimental response compared to the appropriate control group. Tissue extractionIn experiments examining th...

3 Nitrendipine (50 mg kg-', i.p.) and felodipine (10 mg kg-', i.p.) produced around a 75% inhibition of [3H]-isradipine binding 3 h later. Binding of [3H]-nitrendipine to cerebral tissues measured after in vivo injection of the ligand was decreased by nitrendipine (50nmgkg-') and felodipine (10mgkg-') to a similar extent. 4 Nitrendipine (50 mg kg-') prevented the behavioural signs of ethanol withdrawal as measured by handling induced convulsions, but felodipine (10 mg kg-' or 2 mg kg-') did not provide any protection against this effect of ethanol withdrawal. Felodipine (10mg kg-', twice daily) during the course of ethanol treatment also failed to attenuate the withdrawal syndrome. 5 The convulsive response to a mild audiogenic stimulus during ethanol withdrawal was increased following one dose of felodipine (5 mg kg', i.p.) but unaffected by nitrendipine. 6 Injection of Bay K 8644 (60 jig, i.c.v.) produced a significant increase in handling-induced convulsive behaviour. Felodipine (10 mg kg-', i.p.) reduced this behaviour both 60 and 120 min later, while nitrendipine (50 mg kg-') showed a modest reduction only at 120 min. 7 In contrast, nitrendipine (50mg kg-') and felodipine (10 mg kg-') produced similar effects on the hyperexcitability produced by handling following administration of bicuculline. Hexamethonium (8 mg kg -) had no effect on this response.8 No change was found in [3H]-isradipine or ['25l]-w-conotoxin binding to cerebral tissue prepared from ethanol-dependent mice. 9 These results demonstrate that while felodipine and nitrendipine have similar actions on some CNS-mediated effects (raising seizure thresholds to several convulsant drugs), felodipine, in contrast to nitrendipine, has no effect on the ethanol withdrawal syndrome. Suggested explanations for the results include the possibility that nitrendipine may protect against the ethanol withdrawal syndrome via sites other than dihydropyridine receptors: that felodipine has partial agonist actions at dihydropyridine receptors in the CNS or that felodipine has actions which mask its protective effect in ethanol withdrawal.