caa a22 4500 469119292 CHVBK 20180323133134.0 cr unu---uuuuu 170328e19920801xx s 000 0 eng 10.1007/BF02245113 doi (NATIONALLICENCE)springer-10.1007/BF02245113 Chronic infusion of clonidine does not alleviate spontaneous morphine withdrawal symptoms in rats [Elektronische Daten] [J. van der Laan, C. Jansen van't Land] Opiate withdrawal is associated with behavioural symptoms and a sympathetic hyperactivity, the latter being sensitive to clonidine. The central question is whether behavioural symptoms would be also sensitive to clonidine. A rat model was used in which the locomotor activity was measured 24 h a day during the morphine withdrawal phase. Spontaneous withdrawal of morphine reduced strongly the high nocturnal locomotor activity, concomitently decreasing food intake and body weight. Chronic infusion of clonidine (30-120 µg/kg/day) using osmotic minipumps had no effect on the withdrawal symptoms. Higher dosages (250-1000 µg/kg/day) potentiated rather than alleviated the withdrawal symptoms, suggesting anα 1-adrenergic effect of clonidine rather than anα 2-action. Therefore, we studied the action of a more specificα 2-agonist UK-14.304. UK-14.304 was less potent than clonidine in naive animals. It slightly alleviates the decrease of nocturnal activity during spontaneous morphine withdrawal. Furthermore, we have tested whether the effects of high dosages of clonidine could be altered by a specificα 1-antagonist doxazosine. Doxazosine reduced only slightly the potentiation in the decrease in food intake by clonidine during morphine withdrawal. For the other symptoms no interaction between doxazosine and clonidine was found. The data suggest that the use of clonidine in the detoxification of opiate dependent people is based on the suppression of the sympathetic hyperactivity rather than on symptoms with a more behavioural character. Springer-Verlag, 1992 Clonidine nationallicence UK-14.304 nationallicence Behaviour nationallicence Withdrawal nationallicence Doxazosine nationallicence Morphine nationallicence Rat nationallicence van der Laan J. Laboratory for Medicines and Medical Devices, National Institute for Public Health and Environmental Protection, P.O. Box 1, NL-3720 BA, Bilthoven, The Netherlands aut Jansen van't Land C. Laboratory for Medicines and Medical Devices, National Institute for Public Health and Environmental Protection, P.O. Box 1, NL-3720 BA, Bilthoven, The Netherlands aut Psychopharmacology Springer-Verlag 108/3(1992-08-01), 283-288 0033-3158 108:3<283 1992 108 213 https://doi.org/10.1007/BF02245113 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02245113 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- van der Laan J. Laboratory for Medicines and Medical Devices, National Institute for Public Health and Environmental Protection, P.O. Box 1, NL-3720 BA, Bilthoven, The Netherlands aut NATIONALLICENCE 700 1- Jansen van't Land C. Laboratory for Medicines and Medical Devices, National Institute for Public Health and Environmental Protection, P.O. Box 1, NL-3720 BA, Bilthoven, The Netherlands aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 108/3(1992-08-01), 283-288 0033-3158 108:3<283 1992 108 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer