caa a22 4500 465737919 CHVBK 20180323111800.0 cr unu---uuuuu 170327e19900501xx s 000 0 eng 10.1007/BF02253725 doi (NATIONALLICENCE)springer-10.1007/BF02253725 An investigation of the role of 5-hydroxytryptamine in the attenuation of presynaptic α 2-adrenoceptor-mediated responses by antidepressant treatments [Elektronische Daten] [D. Heal, E. Hurst, M. Prow, W. Buckett] 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. Springer-Verlag, 1990 5-Hydroxytryptamine-noradrenaline interactions nationallicence α 2-Adrenoceptor-mediated behaviour nationallicence Sedation nationallicence Hypoactivity nationallicence Clonidine nationallicence Antidepressant effects nationallicence Desipramine nationallicence ECS nationallicence Mice nationallicence Heal D. Research Department, The Boots Company PLC, NG2 3AA, Nottingham, UK aut Hurst E. Research Department, The Boots Company PLC, NG2 3AA, Nottingham, UK aut Prow M. Research Department, The Boots Company PLC, NG2 3AA, Nottingham, UK aut Buckett W. Research Department, The Boots Company PLC, NG2 3AA, Nottingham, UK aut Psychopharmacology Springer-Verlag 101/1(1990-05-01), 100-106 0033-3158 101:1<100 1990 101 213 https://doi.org/10.1007/BF02253725 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02253725 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Heal D. Research Department, The Boots Company PLC, NG2 3AA, Nottingham, UK aut NATIONALLICENCE 700 1- Hurst E. Research Department, The Boots Company PLC, NG2 3AA, Nottingham, UK aut NATIONALLICENCE 700 1- Prow M. Research Department, The Boots Company PLC, NG2 3AA, Nottingham, UK aut NATIONALLICENCE 700 1- Buckett W. Research Department, The Boots Company PLC, NG2 3AA, Nottingham, UK aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 101/1(1990-05-01), 100-106 0033-3158 101:1<100 1990 101 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer