Although morphine remains the primary drug prescribed for alleviation of severe or persistent pain, both preclinical and clinical studies have shown that females require two to three times more morphine than males to produce comparable levels of analgesia. In addition to binding to the neuronal -opioid receptor, morphine binds to the innate immune receptor toll-like receptor 4 (TLR4) localized primarily on microglia. Morphine action at TLR4 initiates a neuroinflammatory response that directly opposes the analgesic effects of morphine. Here, we test the hypothesis that the attenuated response to morphine observed in females is the result of increased microglia activation in the periaqueductal gray (PAG), a central locus mediating the antinociceptive effects of morphine. We report that, whereas no overall sex differences in the density of microglia were noted within the PAG of male or female rats, microglia exhibited a more "activated" phenotype in females at baseline, with the degree of activation a significant predictor of morphine half-maximal antinociceptive dose (ED 50 ) values. Priming microglia with LPS induced greater microglia activation in the PAG of females compared with males and was accompanied by increased transcription levels of IL-1␤ and a significant rightward shift in the morphine dose-response curve. Blockade of morphine binding to PAG TLR4 with (ϩ)-naloxone potentiated morphine antinociception significantly in females such that no sex differences in ED 50 were observed. These results demonstrate that PAG microglia are sexually dimorphic in both basal and LPS-induced activation and contribute to the sexually dimorphic effects of morphine in the rat.

Hamsters are an ideal animal model for a variety of biomedical research areas such as cancer, virology, circadian rhythms, and behavioural neuroscience. The use of hamsters has declined, however, most likely due to the dearth of genetic tools available for these animals. Our laboratory uses hamsters to study acute social stress, and we are beginning to investigate the genetic mechanisms subserving defeat-induced behavioural change. We have been limited, however, by the lack of genetic resources available for hamsters. In this study, we sequenced the brain transcriptome of male and female Syrian hamsters to generate the necessary resources to continue our research. We completed a de novo assembly and after assembly optimization, there were 113,329 transcripts representing 14,530 unique genes. This study is the first to characterize transcript expression in both female and male hamster brains and offers invaluable information to promote understanding of a host of important biomedical research questions for which hamsters are an excellent model.

The basolateral amygdala (BLA) is a critical nucleus mediating behavioral responses after exposure to acute social conflict. Male and female Syrian hamsters both readily establish a stable dominant-subordinate relationship among same-sex conspecifics, and the goal of the current study was to determine potential underlying genetic mechanisms in the BLA facilitating the establishment of social hierarchy. We sequenced the BLA transcriptomes of dominant, subordinate, and socially neutral males and females, and using de novo assembly techniques and gene network analyses, we compared these transcriptomes across social status within each sex. Our results revealed 499 transcripts that were differentially expressed in the BLA across both males and females and 138 distinct gene networks. Surprisingly, we found that there was virtually no overlap in the transcript changes or in gene network patterns in males and females of the same social status. These results suggest that, although males and females reliably engage in similar social behaviors to establish social dominance, the molecular mechanisms in the BLA by which these statuses are obtained and maintained are distinct.

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