Influence of preoptic estradiol on behavioral and neural response to cocaine in female Sprague-Dawley rats.

RATIONALE: Systemic estradiol (E2) increases the behavioral and neural response to cocaine. Where in the brain E2 acts to modulate cocaine response is not entirely clear. Evidence supports a role in this modulation for several candidate regions, including the medial preoptic area (mPOA).

OBJECTIVES: This study examined whether manipulation of E2 in the mPOA modulates differing behavioral responses to cocaine and whether this is reflected in differing levels of c-Fos in the NAc following cocaine administration.

METHODS: Female rats received ovariectomies and bilateral cannulations of the mPOA. They then received either artificial cerebrospinal fluid (aCSF) or E2 microinjections into the mPOA the day before receiving systemic injections of saline or cocaine (5 or 10 mg/kg). Conditioned-place preference (CPP) to cocaine and locomotor activation were then obtained.

RESULTS: Animals receiving 10 mg/kg, but not 5 mg/kg, cocaine developed significant CPP, and those receiving E2 into the mPOA expressed greater CPP than those receiving microinjections of only aCSF at both doses (p < 0.05, d > 0.80). Cocaine also caused significant psychomotor activation, but this was not dependent on microinjection of E2 in the mPOA. Finally, animals that received cocaine had increased NAc core and shell c-Fos relative to animals that received saline, with animals receiving both E2 microinjections and systemic cocaine expressing the highest activation in the caudal NAc, compared to rats receiving aCSF microinjections and systemic cocaine (p = 0.05, d = 0.70).

CONCLUSIONS: These results indicate that E2 in the mPOA facilitates the behavioral response and neural activation that follows cocaine administration. Furthermore, they confirm the close relationship between the mPOA and cocaine response.