• Naotaka Horiguchi, Yukio Ago, Kazuki Asada, Yuki Kita, Naoki Hiramatsu, Kazuhiro Takuma, and Toshio Matsuda.
• Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, 565-0871, Osaka, Japan.
• Psychopharmacology (Berl.). 2013 May 1; 227 (2): 251-61.

RationaleIsolation rearing in rodents causes not only abnormal behaviors which resemble the clinical symptoms of schizophrenia but also hypoalgesia in thermal nociception models. However, the mechanism of the hypoalgesia is not known.ObjectivesThe present study investigated the effect of isolation rearing on acute pain and the descending pain inhibitory pathways in mice.ResultsRearing in isolation for 6 weeks from post-weaning reduced pain sensitivity in the hot plate test and acetic acid-induced writhing test. Isolation rearing also reduced the intraplantar capsaicin-induced licking behavior. Capsaicin increased c-Fos expression, a neuronal activity marker, in the spinal cord and primary somatosensory cortex both in group- and isolation-reared mice, but this effect did not differ between groups. On the other hand, c-Fos expression in the anterior cingulate cortex, periaqueductal gray matter, and rostral ventromedial medulla, but not in the spinal cord or somatosensory cortex, was enhanced by isolation rearing. Systemic administration of WAY100635 (serotonin (5-HT)1A receptor antagonist), but not of ketanserin (5-HT2 receptor antagonist), prazosin (α1-adrenoceptor antagonist), or yohimbine (α2-adrenoceptor antagonist), attenuated isolation rearing-induced hypoalgesia in capsaicin-induced licking behavior. Attenuation of isolation rearing-induced hypoalgesia was also observed following the intrathecal injection of WAY100635. Naloxone, an opioid receptor antagonist, did not affect the hypoalgesia in isolation-reared mice.ConclusionsThese findings suggest that isolation rearing causes hypoalgesia in mouse models of acute pain and imply that the spinal 5-HT1A receptor activation probably through descending serotonergic inhibitory pathway is involved in isolation rearing-induced hypoalgesia.

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