Behavioural Brain Research, 59 (1993) 83-93 © 1993 Elsevier Science B.V. All rights reserved. 0166-4328/93/$06.00 BBR 01528 83 Studies on the behavioral activation produced by stimulation of GABAB receptors in the median raphe nucleus David Wirtshafter*, Thomas R. Stratford**, Mark R. Pitzer Department (?f P.~3,cholog),, M/C 285, The University (~/'Illinois at Chicago, Chicago, IL 60680 (USA ~ (Received 10 May 1993) (Revised version received 13 August 1993) (Accepted 19 August 1993) Key words: Median raphe nucleus; Dorsal raphe nucleus; Ventral tegmental area; Baclofen; 7-Aminobutyric acidB; Locomotor activity; Feeding; Drinking; Serotonin; Dopamine Injections of the GABA R agonist baclofen into the median raphe nucleus (MR) resulted in marked hyperactivity and in increases in food and water intake by non-deprived animals. The locomotor effects of baclofen were stereospecific and could be antagonized by coinjection of the GABA R antagonist 2-hydroxysaclofen. Hyperactivity was produced by lower doses of baclofen, at shorter latencies, when the drug was injected into the MR than when it applied to the dorsal raphe nucleus (DR) or the ventral tegmental area (VTA). The locomotor response to intra-MR baclofen was unaltered in animals pretreated with the serotonin synthesis inhibitor p-chlorophenylalanine. Finally, intra-MR injec- tions of baclofen produced a large increase in dopamine metabolism in the nucleus accumbens and striatum but failed to alter hippocampal or striatal serotonin metabolism. These findings suggest that baclofen may produce increases in activity and ingestive behavior as a result of an action on non-serotonergic cells in the MR. INTRODUCTION Considerable evidence indicates that the median raphe nucleus (MR) may exert an important control over a variety of behaviors. For example, electrolytic lesions of the MR lead to hyperactivity 2"5'14"3°'32"~9, hy- perdipsia 1,~l, and to disturbances in the performance of a number of instrumental tasks 3'4'5. Although most early workers assumed that these effects were secondary to the depletions in forebrain serotonin produced by the lesions, later studies employing specific neurotoxins demonstrated that non-serotonergic cells within the MR must be damaged for many of the effects of elec- trolytic lesions to be reproduced 2-4'13'16'18~3°'32. It is possible that damage to fibers of passage may also play a role in some of the effects of non-specific lesions 2. Many recent studies of the MR have utilized the method of intracranial microinjections of various neu- rotransmitter agonists and antagonists. An important advantage of this technique is that it minimizes the * Corresponding author. Fax: (1) (312) 413-4122. ** Present address: Dept. of Psychiatry, Cornell Medical Center, 21 Bloomingdale Rd., White Planes, NY 10605, USA. likelihood of effects due to an involvement of fibers of passage. Intra-MR injections of the GABA A agonist muscimol have been studied in the most detail. These injections result in very pronounced hyperactivity and in robust increases in food and water intake by non- deprived a n i m a l s 2v-29"4°'41"44"45"5°-52"56. All of these ef- fects are precisely localized to the MR and much smaller effects are seen with injections into adjacent struc- tures 2s'4°'44'5°. Intra-MR muscimol injections also re- sult in an acceleration of dopamine metabolism in the nucleus accumbens 37'52"5~ and a depression of seroto- nin turnover in several forebrain s t r u c t u r e s ~2"3~52"5~'. Although these latter results suggest that intra-MR muscimol injections inhibit the firing of serotonin con- taining neurons, neither the hyperactivity and increased ingestive behavior nor the increases in dopamine turn- over produced by muscimol appear to be dependent on mechanisms ,k The simplest intact serotonergic 41 ~ 1.56 explanation of these findings is that GABA a receptors are found both on serotonergic and non-serotonergic neurons within the MR and that inhibition of the non- serotonergic cells plays a preeminent role in mediating the behavioral effects of muscimol injections. In the current report we examined the behavioral and biochemical effects produced by intra-raphe injections