DESENSITIZATION AND RESENSITIZATION OF NOREPINEPHRINE RELEASE IN THE RAT HIPPOCAMPUS WITH REPEATED NICOTINE ADMINISTRATION

Desensitization of norepinephrine release was investigated with repeat ed intravenous (i.v.) infusions of nicotine and in vivo microdialysis of the hippocampus. At 100 min intervals, rats received three infusion s of one of the following doses of nicotine: 0.045, 0.09 or 0.135 mg/k g, Doses of 0.09 mg/kg or higher increased norepinephrine release (F = 2.41, P < 0.05). However, the norepinephrine response to the second o r third infusion was significantly I educed, compared to the first. Th e extent of desensitization and rate of resensitization was investigat ed further by administering consecutive infusions of nicotine (0.135 m g/kg) 40, 60, 100 or 200 min apart. Less norepinephrine was released a fter a second nicotine infusion given 40 to 100 min later, but this wa s not reduced further by a third infusion. Norepinephrine release was unchanged with a 200 min inter-infusion interval. Therefore, in the hi ppocampus, maximal desensitization of nicotine-stimulated norepinephri ne release occurs as early as 40 min and persists for at least 100 min ; thereafter, resensitization becomes the dominant process. (C) 1998 E lsevier Science Ireland Ltd.