Ž . Brain Research Reviews 25 1997 397–406 Short review Sex differences in pain-induced effects on the septo-hippocampal system Anna Maria Aloisi ) Institute of Human Physiology, UniÕersita degli Studi di Siena, Via Aldo Moro, I-53100 Siena, Italy ` Accepted 19 August 1997 Abstract In addition to its role in the modulation of functions such as arousal and attention, learning and memory, the limbic system has repeatedly been described to be involved in the regulation of several behavioral aspects concerning the adaptation to aversive situations, including pain. A key role in these processes seems to be played by the septo-hippocampal system. This paper, far from being a comprehensive review of all the data available about the limbic system, describes some of the circuits participating in the septo-hippo- campal system, with the aim of contributing to an understanding of the sex differences in the behavioral, hormonal and neuronal responses to aversive stimuli. It will appear that the complex anatomical and functional interactions between the different neurotrans- mitters acting at this level prevent one from indicating a certain substance as more important than others in determining a difference between the two sexes. This leads to the conclusion that the septo-hippocampal formation in toto plays a key role in determining the sex differences in the ‘pain experience’. q 1997 Elsevier Science B.V. Keywords: Limbic system; Male; Female; Hormone; ACh Contents 1. Introduction ...................................................................... 398 2. Sex differences in the behavioral responses to painful stimuli ............................................ 398 3. Sex differences in the anatomy and physiology of the septo-hippocampal system ................................. 399 3.1. Cholinergic system ............................................................... 399 3.2. Aminergic systems ............................................................... 400 Ž . 3.2.1. Noradrenalin NA ............................................................ 400 Ž . 3.2.2. Serotonin 5-HT ............................................................. 400 3.3. Opioids ...................................................................... 401 3.4. Sex hormones .................................................................. 401 3.5. Neurosteroids and GABA ............................................................ 401 3.6. Glucocorticoids ................................................................. 402 4. Sex differences in the septo-hippocampal responses to aversivestimuli ....................................... 402 5. Conclusions ...................................................................... 403 Acknowledgements.................................................................... 403 References ........................................................................ 403 ) Ž . Corresponding author. Istituto Fisiologia Umana, Via Aldo Moro, 53100 Siena Italy. Fax: q39 577 227037; E-mail: aloisi@unisi.it 0165-0173r97r$32.00 q 1997 Elsevier Science B.V. All rights reserved.