Sex differences in behavioral and neural cross-sensitization and escalated cocaine taking as a result of intermittent social defeat stress in rats.
Abstract: Brief episodes of social stress can result in cross-sensitization to
cocaine in rodents, characterized by augmented locomotor activation, dopamine (DA) levels
in the nucleus accumbens (NAc), and cocaine taking during a 24 hour "binge" in male rats.
However, females are more vulnerable than males at each phase of cocaine addiction, and
while these sex differences have been replicated ... read morein rats, the role of social stress in
females has remained largely neglected. Long-Evans rats were subjected to four episodes, 72
hours apart, of social defeat by an aggressive resident of the same sex. Ten days later,
rats were either assessed for (1) behavioral sensitization as determined by locomotor
activity in response to acute cocaine (10 mg/kg, ip) (2) DA sensitization to acute cocaine
as measured by in vivo microdialysis of the NAc, or (3) intravenous self-administration of
cocaine (0.3 mg/kg/infusion, fixed ratio 1) in an unlimited access "binge". Both stressed
males and females showed elevated locomotor activity 5-10 minutes after cocaine injection,
but in females the effect was both larger and more prolonged, regardless of estrous cycle
phase. While stressed males showed a significant increase in extracellular DA in the NAc
compared to non-stressed males, there was no difference in the percent baseline DA levels
between stressed males and both groups of females. However, the augmentation in
extracellular DA persisted in stressed females, whereas it returned to baseline within 30
min for all other groups. Finally, while stressed males and all females had similar cocaine
intake during the first 24 hrs of the cocaine binge, stressed females had a significantly
longer "binge". These data suggest that socially stressed females exhibit a more robust and
longer lasting behavioral cross-sensitization, as well as more disregulated cocaine taking,
possibly due to alterations in the dopaminergic response in the nucleus accumbens.
Furthermore, estradiol appears to play a facilitatory role in both behavioral and
dopaminergic sensitization, although future studies need to assess these effects more
Thesis (M.S.)--Tufts University, 2012.
Submitted to the Dept. of Psychology.
Advisor: Klaus Miczek.
Committee: Joseph DeBold, and Emmanuel Pothos.
Keywords: Experimental psychology, Physiological psychology, and Neurosciences.read less