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An investigation of the role of 5-hydroxytryptamine in the attenuation of presynapticα 2-adrenoceptor-mediated responses by antidepressant treatments

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Abstract

Changes in the function of presynapticα 2-adrenoceptors in the brain were assessed by rating the hypoactivity (sedation) response of mice to clonidine (0.1 mg/kg). A single injection of 5,7-dihydroxytryptamine (5,7-DHT, 75 µg ICV) or administration ofp-chlorophenylalanine (PCPA; 200 mg/kg) daily for 11–15 days produced 62–77% reductions in brain 5-HT concentrations and marked supersensitivity of 5-HT2 receptor function, as indicated by the enhancement of the head-twitch response to 5-methoxy-N,N-dimethyltryptamine (2 mg/kg). Clonidine-induced hypoactivity was moderately enhanced after 5,7-DHT lesioning, but not after repeated PCPA injection. In addition, 5,7-DHT lesioning prevented the adaptive attenuation of thisα 2-adrenoceptor-mediated response produced by daily injection of desipramine (10 mg/kg) for 14 days, but had no effect on the reduction caused by five electroconvulsive shocks (ECS, 200 V, 2 s) spread over 10 days. In contrast, repeated PCPA treatment did not prevent the reduction of clonidine-induced hypoactivity produced by repeated desipramine or ECS administration. Together, these results indicate that 5-HT (or possibly a cotransmitter contained within 5-hydroxytryptamine neurones) influences presynapticα 2-adrenoceptor function. Furthermore, an intact 5-HT neuronal input is a prerequisite for the attenuation of clonidine-induced hypoactivity by desipramine, but not ECS. The probable explanation for a contrasting requirement for a functional 5-HT input is that desipramine and ECS induce this common adaptive response by different pharmacological mechanisms.

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  1. Research Department, The Boots Company PLC, NG2 3AA, Nottingham, UK

    D. J. Heal, E. M. Hurst, M. R. Prow & W. R. Buckett

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  1. D. J. Heal
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  2. E. M. Hurst
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  3. M. R. Prow
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  4. W. R. Buckett
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Heal, D.J., Hurst, E.M., Prow, M.R. et al. An investigation of the role of 5-hydroxytryptamine in the attenuation of presynapticα 2-adrenoceptor-mediated responses by antidepressant treatments. Psychopharmacology 101, 100–106 (1990). https://doi.org/10.1007/BF02253725

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  • DOI: https://doi.org/10.1007/BF02253725

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