Effects of ventral hippocampal lesion on thermal and mechanical nociception in neonates and adult rats Hassen A. Al Amin, 1 Samir F. Atweh, 2 Suhayl J. Jabbur 3 and Nayef E. Saade ´ 3,4 1 Department of Psychiatry, Faculty of Medicine (FM), American University of Beirut (AUB), Beirut, Lebanon 2 Department of Internal Medicine, FM, AUB, Beirut, Lebanon 3 Department of Physiology, FM, AUB, Beirut, Lebanon 4 Department of Human Morphology, FM, AUB, Beirut, Lebanon Keywords: animal model, hot plate, neurodevelopment, paw pressure, tail flick Abstract The proper maturation of the hippocampus is essential for the development of different behaviours, including memory, pain responses and avoidance. The mechanisms involved in the neurodevelopment of nociception have also been implicated in several neuropsychiatric disorders. The neonatal lesion of the ventral hippocampus (VH) in rats, an animal model of schizophrenia, can be utilized to study the developmental neurobiology of animal behaviour. We examined the nociceptive responses in this animal model at different stages of development. Rat pups were lesioned at postnatal day 7 by injecting ibotenic acid into the VH bilaterally, and then tested for thermal and mechanical nociception at the age of 35, 65 and 180 days. The nociceptive tests used were the hot plate (HP), paw pressure (PP) and tail flick (TF) tests. Another group of adult rats had the same lesion in the VH and then underwent the same tests at 28, 56 and 168 days post-lesions. When compared with sham controls, the rats with neonatal VH lesion showed decreased latency for the HP and PP tests only after puberty. The TF test showed significant increase in latency for both groups at age 65 and 180 days. The adult rats with VH lesion showed no major changes over all periods of testing. These results suggest that early lesion of VH can alter the development of the neural mechanisms involved in the processing of thermal and mechanical nociception. Introduction The hippocampal formation is known to play a major role in the emotional and avoidance components of nociception (Melzack & Casey, 1968). Microinjection of lidocaine (McKenna & Melzack, 1992) or the competitive N-methyl-d-aspartate (NMDA) receptor antagonist AP5 (McKenna & Melzack, 2001) into the hippocampal dentate gyrus produces analgesia in the formalin test. Using the same test it has been shown that formalin injection decreases the Fos protein expression in the CA1, CA3 and dentate gyrus mainly in the posterior- ventral regions of hippocampus (Khanna et al., 2004). Norepinephrine increases the nociceptive responses in hot plate (HP) and footshock tests when injected into the ventral hippocampus while serotonin has opposite effects (Gage & Springer, 1981). The cholinergic septo- hippocampal pathway has been shown to be involved in the cerebral mechanisms related to nociception (Dutar et al., 1985). Other anatomical and neuroimaging studies have also demonstrated the importance of hippocampus in the central processing and modulation of nociception (Lathe, 2001; Ploghaus et al., 2001). Clinical observations showed that the hippocampus is involved in processing of noxious stimuli (Delgado, 1955) and that hippocampal lesion can alter the perception of nociception and partially alleviate chronic pain (Gol & Faibish, 1967; Hebben et al., 1985). It is also not clear how neurodevelopment and ageing can affect nociceptive behaviours. Several studies have highlighted the develop- ment of nociception and how it is regulated by the neurodevelopment of peripheral, spinal and supraspinal mechanisms (for review see Narsinghani & Anand, 2000). The thermal, mechanical and inflam- matory nociceptive responses in rat pups suggest increased sensitivity as assessed by the HP (Hu et al., 1997), tail flick (TF; Falcon et al., 1996), paw pressure (PP; Nica ˆk, 1971) and formalin tests (McLaughlin et al., 1990). This hypersensitivity decreases with the maturation of different neuronal mechanisms within the pain system (Woolf & Salter, 2000). Other studies showed that ageing is also associated with several neurochemical and neuroanatomical changes that can ultimately affect the nociceptive responses (for review see Gagliese & Melzack, 2000). The hippocampus is well known to be very sensitive to hypoxia, anoxia and other metabolic or pharmacological insults, especially during early stages of development. The neonatal lesion of the ventral hippocampus (VH), used as an animal model of schizophrenia, has been shown to lead to several behavioural abnormalities in adulthood that could be related to possible developmental dysfunction of temporolimbic circuitry (Weinberger & Lipska, 1995). Furthermore, several studies have suggested that the neurochemical mechanisms implicated in schizo- phrenia are also involved in the pathological alterations of pain perception (see review by Lautenbacher & Krieg, 1994). The purpose of this study is to test the effects of VH lesion in rat pups and adults on acute mechanical and thermal nociceptive responses at different stages of development using the HP, PP and TF tests. Correspondence: Dr H. A. Al Amin, as above. E-mail: ha03@aub.edu.lb Received 10 March 2004, revised 28 August 2004, accepted 20 September 2004 European Journal of Neuroscience, pp. 1–8, 2004 ª Federation of European Neuroscience Societies doi:10.1111/j.1460-9568.2004.03762.x