ELSEVIER Neuroscience Letters 215 (1996) 201 204 NEUROSCIEHC[ IEIT[BS Induction of interleukin-1/3 and interleukin-1 receptor antagonist mRNA by chronic treatment with various psychotropics in widespread area of rat brain Eiji Suzuki a'*, Futoshi Shintani a, Shigenobu Kanba a, Masahiro Asai a, Toshio Nakaki b aDepartment of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan bDepartment of Pharmacology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan Received 29 May 1996; revised version received 12 August 1996; accepted 14 August 1996 Abstract We investigated whether psychotropics orally administered to rats affect levels of interleukin-1/3 (IL-1/3) and interleukin-l receptor antagonist (IL-1Ra) mRNA in the hypothalamus, hippocampus, frontal cortex, and brain stem, using a reverse transcription-polymerase chain reaction method. The psychotropics tested were chlorpromazine, haloperidol, imipramine, maprotiline, fluvoxamine, and diaze- pam. Treatment for 28 days raised the levels of both mRNAs. The increase in IL-1Ra mRNA was 6-112 times larger than that of IL-I/3 mRNA in most brain regions examined. These results suggest that chronic treatment with psychotropics causes greater amplifying effects on IL-IRa mRNA than IL-1/3 mRNA in the brain. Keywords: Interleukin-l/3; Interleukin-1 receptor antagonist; mRNA; Psychotropics; Brain; Adrenal gland; Hypothalamus; Reverse transcription-polymerase chain reaction Administration of interleukin-1 (IL-l) into the brain elicits a number of behavioral responses in rats and mice, which are similar to those observed in stress- exposed animals [9]. IL-1 receptor antagonist (IL-1Ra) prevents IL-1/3-induced behavioral responses [1]. On the other hand, treatment with antidepressants, neuroleptics and anxiolytics antagonizes the stress-induced behavioral changes, which are regarded as models of psychiatric dis- eases [5,8,18]. These actions of psychotropics have been interpreted as being a result of monoamine turnover attenuation [7,19]. Recently, we have reported that IL- 1Ra prevents the IL-1/3-induced release of monoamines [15] and reviewed several lines of evidence that IL-1 acts as a putative neurotransmitter [16]. Therefore, we hypothesized that IL-1 receptor agonism and antagonism play a role in the clinically relevant effects of psychotro- pics. Herein we examined whether acute and chronic administration of various psychotropics, including chlor- promazine (CP), haloperidol (HAL), imipramine (IMP), maprotiline (MPR), fluvoxamine (FVX), and diazepam * Corresponding author. Tel.: +81 3 33531211, ext. 2455; fax: +81 3 53790187. (DAZ), to rats affect the levels of IL-1/3 and IL-lRa mRNA in various brain regions and the adrenal gland (AG). Five week old male Sprague-Dawley rats (Sankyo Laboservice, Tokyo, Japan) were housed in a tempera- ture-controlled room (23-25°C) under a 12 h reversed light]dark schedule. Food and water were provided ad libitum at all times. Drugs were mixed with the food start- ing at 6 weeks of age at the following daily dosages (in mg/ kg): CP 10; HAL 1; IMP 50; MPR 50; FVX 50; DAZ 2. There were no statistically significant differences in food consumption or in weight gain between the control ani- mals, which were given powder food without drugs, and those treated with any of the drugs (data not shown). Treat- ment periods were 1, 4 and 28 days (acute, subacute and chronic, respectively). For RNA extraction, groups of four rats were decapitated under light anesthesia with ether, and, the brain and AG were quickly removed. The brains of chronically treated rats were dissected into the follow- ing regions; hypothalamus (HY), hippocampus (HIP), frontal cortex (FC), and brainstem (BS). The HY and HIP were also examined in acutely and subacutely treated rats. 0304-3940/96/$12.00 © 1996 Elsevier Science Ireland Ltd. All rights reserved Pll S0304-3940(96) 12985-2