Ž . Brain Research 838 1999 95–103 www.elsevier.comrlocaterbres Research report The effects of median raphe electrical stimulation on serotonin release in the ´ dorsal hippocampal formation of prenatally protein malnourished rats David J. Mokler a, ) , Joseph D. Bronzino b , Janina R. Galler c , Peter J. Morgane a,c a Department of Pharmacology, College of Osteopathic Medicine, UniÕersity of New England, Biddeford, ME 04005, USA b Department of Engineering, Trinity College, Hartford, CT 06106, USA c Center for BehaÕioral Department and Mental Retardation, Boston UniÕersity School of Medicine, Boston, MA 02118, USA Accepted 25 May 1999 Abstract Our previous work had shown an enhanced inhibition in the hippocampal formation of prenatally protein malnourished rats. We have Ž . also found a diminishment in 5-hydroxytryptamine 5-HT fibers in the hippocampal formation of malnourished rats as well as increased levels of 5-HT in the brain. The purpose of the present study was to determine 5-HT release in the dorsal hippocampal formation Ž . following electrical stimulation of the median raphe nucleus MRN in unanesthetized prenatally malnourished rats. Stimulation of this ´ nucleus at 20 Hz in malnourished rats resulted in a significantly diminished release of 5-HT compared to well-nourished rats. The latter group showed a lesser, though still significant, decrease in 5-HT release following raphe stimulation. Basal release of 5-HT prior to ´ stimulation was significantly higher in malnourished rats as compared to well-nourished controls. This may be the result of a decreased density of 5-HT neurons leading to a diminished control of release. Stimulation of the MRN in behaving malnourished animals may markedly affect the recurrent negative feedback collaterals onto somatodendritic 5-HT and 5-HT autoreceptors thus enhancing the 1A 1D inhibitory effects of stimulation of the median raphe on 5-HT release. Studies are underway to examine the sensitivity of both the ´ somatodendritic and terminal 5-HT autoreceptors in malnourished animals, in order to understand possible mechanisms for our findings. q 1999 Elsevier Science B.V. All rights reserved. Keywords: In vivo microdialysis; 5-HT autoreceptors; 5-Hydroxytryptamine; Hippocampal formation; Vigilance state plasticity; Raphe–hippocampal ´ system 1. Introduction The present studies are aimed at gaining insights into possible mechanisms of the effects of prenatal protein malnutrition on GABA-mediated inhibitory processes in the hippocampal formation. By examining the release of serotonin in the hippocampal formation following raphe ´ stimulation in well-nourished compared to malnourished rats, we can assess how prenatal malnutrition affects the functional integrity of the raphe–hippocampal system. The ´ hippocampal formation offers a unique model system for evaluation of brain insults such as prenatal malnutrition on w x synaptic function and plasticity. In previous studies 31 we found that electrical stimulation of the midbrain raphe ´ Ž . in behaving awake rats results in a significant decrease in serotonin release in the dorsal hippocampal formation. ) Corresponding author. Fax: q1-207-286-9493; E-mail: dmokler@mailbox.une.edu These findings in awake rats are opposed to previous studies using anesthetized rats in which electrical stimula- tion of the midbrain raphe nuclei resulted in increased ´ serotonin release in the hippocampal formation w x 29,31,41,42 . w x In our earlier study 31 we described the considerable complexities of the raphe–hippocampal serotonergic sys- ´ tem including the multiple feedback fibers onto somato- dendritic 5-HT and 5-HT autoreceptors in the raphe ´ 1A 1D Ž . nuclei, various types of 5-hydroxytryptamine 5-HT re- Ž ceptors on terminals of 5-HT neurons 5-HT and 5- 1B . HT , including details of the circuitry of both midbrain 1D raphe nuclei and synapses on interneurons in the hip- ´ Ž . pocampal formation Figs. 1 and 2 . In the present study we have concentrated primarily on the MRN which pro- jects largely to the dorsal hippocampal formation and medial septal nucleus. In our series of electrophysiological studies we have clearly shown a diminished plasticity in the hippocampal formation of prenatally malnourished rats by examining 0006-8993r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S0006-8993 99 01677-7