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

Abstract

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...

Interaction of Sertraline and Nimodipine on Some Behavioural Tests in Rats

“…This result indicates an inhibitory effect on the antidepressant effect of sertraline by repeated doses of nimodipine administration. The inhibition revealed by repeated doses of nimodipine administration may be the consequence of the reported role of L-type calcium channels on the release of neurotransmitters [18] and the complex effects of ccas on serotonin functions in rodents [19]. In this study, we also observed that there was no significant difference between groups in the time spent in closed arms in the elevated plus maze test.…”

“…Furthermore, Srivastava et al and aburawi et al did not use nimodipine in their study, instead they used nifedipine as an L-type dihydropyridine derivate cca. although both nifedipine and nimodipine are dihydropyridine derivate L-type ccas, they may have different effects on neurotransmitter functions [19].…”

The effect of dihydropyridine calcium channel agents on 5-HT metabolism in the CNS of the rat

“…Other authors have also reported that dihydropyridines exert complex changes in 5-HT function. Recently, Green et al(1990) indicated that pretreatment of rats with felodipine. 15 min before tranylcypromine.…”

Enhanced 5-HT2A Receptors in Brain Stem and ALDH Activity in Brain Stem and Liver: 5-HT2A Regulation on ALDH in Primary Hepatocytes Cultures In Vitro

“…5-HT 2A receptor binding assay was done according to the modified procedure of Green et al [22]. The brain stem was homogenized in 10 volumes of ice cold 0.32 M sucrose in Potter-Elvejhem homogeniser.…”