Behavioural hyperactivity in rats treated with selective monoamine oxidase inhibitors and LM 5008, a selective 5‐hydroxytryptamine uptake blocker

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Abstract
1 The administration of 4-[2-(3-indolyl)ethyl]piperidine (LM 5008), a selective 5-hydroxytryptamine (5-HT) uptake blocker to rats pretreated with tranylcypromine (Tcp) resulted in a behavioural syndrome of locomotor hyperactivity which is indistinguishable from that following combined treatment with Tcp and l-tryptophan. 2 A similar behavioural response was elicited by the administration of LM 5008 to rats pretreated with 5-hydroxytryptophan. 3 The response to LM 5008 after monoamine oxidase (MAO) inhibition was abolished by pretreatment with p-chlorophenylalanine, indicating the involvement of 5-HT in producing the hyperactivity syndrome. 4 The administration of imipramine and chlorimipramine in combination with Tcp also resulted in hyperactivity, but these drugs were much less potent than LM 5008 in producing the syndrome. 5 In contrast to l-tryptophan, which can produce hyperactivity only after the inhibition of both type A and type B MAO, LM 5008 can elicit the syndrome after selective inhibition of MAO type A only but not after inhibition of MAO type B. 6 The behavioural results indicate that when MAO type A is inhibited, LM 5008 treatment elicits hyperactivity by preventing the availability of 5-HT to be metabolized by MAO-B component.

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