Behavioral sensitization to cocaine after a brief social stress is accompanied by changes in Fos expression in the murine brainstem

The objective of the present study was to determine how c-fos gene expression in brainstem structures after a brief episode of social defeat stress is related to behavioral sensitization to cocaine challenge. Social stress was defined as defeat in a brief confrontation with an aggressive resident mouse and subsequent 20-min exposure to the resident's threats behind a protective screen. Mice were treated with cocaine (40 mg/kg, i.p.) immediately or 1 week after social defeat stress. Fos-like immunoreactive (Fos-LI) cell nuclei were analyzed in the ventral tegmental area (VTA), dorsal raphe nucleus (DR), periaqueductal grey area (PAG) and locus coeruleus (LC). One episode of social stress induced behavioral sensitization to cocaine as indicated by an augmented locomotor response to a challenge injection 7 days after a single defeat. In naive mice, social stress markedly increased the number of Fos-LI nuclei in the DR, PAG and LC, but not in the VTA. Similarly, cocaine administration resulted in a significantly increased number of Fos-LI nuclei in the same areas. Administration of cocaine immediately following social defeat significantly reduced the number of Fos- LI nuclei in the DR, PAG and LC. Cocaine-induced Fos expression returned in the PAG and DR, but not in the LC, 1 week after social stress. In conclusion, the present results suggest that the presence of brainstem Fos be related to the ability to express stress-induced behavioral sensitization to cocaine.