c-fos expression, behavioural, endocrine and autonomic responses to acute social stress in male rats after chronic restraint: modulation by serotonin.

The effects in male rats of serotonin depletion (using the neurotoxin 5,7-dihydroxytryptamine) on the cross-sensitization of an acute social stress (defeat by a larger resident male) by previous repeated restraint stress (10 days, 60 min per day) was studied. Previous restraint increased freezing responses during social defeat in sham-operated rats, but this was not observed in those with depleted serotonin (83% or more in different regions of the brain). In contrast, neither heart rate (tachycardia) nor core temperature responses (hyperthermia) were accentuated in previously restrained rats (i.e. neither showed heterotypical sensitization), and neither adapted to repeated restraint (there is a hypothermic core temperature response during restraint). Corticosterone levels, which did adapt, nevertheless did not show accentuated responses to social defeat in previously restrained rats, though samples could only be taken 60 min after defeat. c-fos expression in the central nucleus of the amygdala 60 min after social defeat was increased by previous restraint. No other areas examined in the hypothalamus (e.g., paraventricular nucleus) or brainstem (e.g., solitary nucleus) showed differences related to previous restraint. Serotonin depletion reduced the expression of c-fos in the frontal cortex, lateral preoptic area, medial amygdala, central gray, medial and dorsal raphe, and locus coeruleus after social stress, but this was not altered by previous restraint. These results show that serotonin depletion has selective effects on the cross-sensitization of responses in previously stressed rats to a heterotypical stressor.