Sex differences in behavioral and neural cross-sensitization and escalated cocaine taking as a result of intermittent social defeat stress in rats.
Holly, Elizabeth.
2017-04-18T13:57:10.857Z
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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 in r... read moreats, 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 directly.
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 - ID:
- qv33s819h
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