Long-term behavioral and neuronal cross-sensitization to amphetamine induced by repeated brief social defeat stress: Fos in the ventral tegmental area and amygdala
Section snippets
Animals
The subjects were 82 male Long-Evans rats (Charles River Laboratories, Wilmington, MA, USA), weighing 280–320 g upon arrival. They were housed individually under a reverse 12-h light/dark cycle (lights off at 08:00 h) with unlimited access to food (Purina Rodent Diet, Brentwood, MO, USA) and water. Stimulus male rats, termed “residents,” were pair-housed with females in a separate room, where social defeat procedures were carried out as described below. Each resident was selected after being
Behavioral effect of social stress
Four episodes of social defeat stress alone did not change baseline locomotor activity (frequency of walking) in response to saline injection 17 or 70 days after the first defeat (Fig. 1). However, a single challenge with amphetamine revealed significant effects of previous social defeat stress. Amphetamine (1 mg/kg) induced significantly higher frequencies of walking activity, which was measured 25 min after administration, in stressed animals either 17 days (F1,51=9.1; P<0.005) or 70 days (F
Discussion
The present results demonstrate that repeated brief episodes of social defeat stress induce behavioral sensitization to d-amphetamine, which was long-lasting as evidenced by the augmented response to d-amphetamine challenge 2 months after social defeat stress. Repeated exposure to social defeat stress produced significant Fos-LI labeling in mesocortical dopaminergic areas 1 week after stress termination, but this functional activation was not increased further after d-amphetamine challenge. d
Acknowledgements
This research was supported by USPHS research grants to E.M.N. (DA14327), K.A.M. (DA02632) and R.P.H. (MH066954).
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