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Involvement of 5-hydroxytryptamine and dopamine neurones in the behavioural effects of α-methyl

Involvement of 5-hydroxytryptamine and dopamine neurones in the behavioural effects of α-methyl

  1. Calliope
    Neuropharmacology, 1980, Vol.19(8), pp.691-698

    Marsden, C.A.

    α-Methyltryptamine (10 mg/kg) produced a two-phased behavioural response in the rat. The first phase consisted of responses such as hind limb abduction, forepaw treading, lateral head weaving and Straub tail and lasted up to 90 min. The second phase of the behavioural response lasted up to 4 hr and consisted of marked running and exploratory activity. p-Chlorophenylalanine (150 mg/kg), which depletes brain 5 hydroxytryptamine, prevented both phases of the behavioural response. α-Flupenthixol (0.4 mg/kg) a dopamine receptor antagonist also attenuated both phases of the response. Metergoline (2 mg/kg), a 5 hydroxytryptamine receptor antagonist, abolished the initial phase of the response but had no effect on the second phase and the animals showed well co-ordinated exploratory behaviour throughout the experimental period. Fluoxetine (10 mg/kg), which probably inhibited the uptake of α-methyltryptamine into 5 hydroxytryptamine neurones, prevented the initial response and reduced the second phase. Pimozide (0.3 mg/kg), another dopamine receptor anatgonist, had no effect on the first part of the response but significantly reduced the second exploratory phase. There was no significant change in brain 5-hydroxytryptamine and 5 hydroxyindoleaetic acid during the time course of the initial behavioural response. In vivo electrochemical recordings, from the striatum and hippocampus, indicated an increase in extraneuronal amine, probably mainly 5-hydroxytryptamine, during the initial phase.

    The results indicate that the initial behavioural response is primarily due to a pre-synaptic action of α-methyltryptamine on 5-hydroxytryptamine neurones but with the participation of dopamine neurones. The second phase involved more general stimulation of dopamine neurones, but an intact 5-hydroxytryptamine neuronal system appears essential.