Ovarian Hormones Modulate Cocaine‐Induced Locomotor and Stereotypic Activity

Abstract

Interactions between ovarian hormones and cocaine may underlie gender and estrous cycle differences in cocaine‐induced behavioral and neurochemical alterations. The aim of this study was to further understand how ovarian hormones modulate cocaine‐induced behavioral alterations. Ovariectomized rats received acute or chronic saline or cocaine (15 mg/kg i.p.) administration and were further subdivided into one of four hormone‐treatment conditions: cholesterol (vehicle‐control), estrogen, progesterone, or estrogen+progesterone. Overall, acute and chronic cocaine administration increased all locomotor measurements (total locomotor, ambulatory, and rearing counts). Estrogen administration augmented cocaine‐induced increases in ambulatory and rearing activity. After chronic cocaine administration, rats in the vehicle‐control group developed behavioral tolerance (exhibited by a decrease in activity) in rearing and ambulatory activity. Estrogen replacement not only prevented the development of tolerance in ambulatory and rearing activities, but also enhanced total locomotor activity (sensitization) in response to chronic cocaine. Progesterone treatment did not alter the behavioral responses to acute or chronic cocaine administration. Estrogen+progesterone‐treated animals had higher counts of locomotor activity in response to chronic cocaine than did vehicle‐control or progesterone‐treated rats. In stereotypic behaviors, the different hormonal treatments did not affect activity in cocaine‐ or saline‐treated rats after acute or chronic drug administration. Plasma levels of cocaine did not change after different hormonal treatments. Interestingly, animals' coadministered chronic cocaine and estrogen had higher levels of corticosterone than did nonestrogen cocaine‐treated rats. Thus, it is likely that alterations in HPA activation may underlie the observed behavioral differences. In summary, these data suggest that there are interactions between ovarian hormones and cocaine‐induced behavioral alterations in female rats, and they extend previous results by showing that estrogen and progesterone affect the development of sensitization.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

“…Previous studies have also found that ovariectomy decreases or delays behavioral sensitization to cocaine and also decreases self-administration behavior in female rats (12). However, although previous studies have not found a significant increase in stereotypy behavior after acute or repeated cocaine administration in OVX rats (9,29), we found that acutely administered or cocaine-sensitized OVX rats had more stereotypy behaviors than control (saline-injected) rats. Curiously, exogenous progesterone, with or without estradiol, abolished these stereotypy behaviors in the OVX rats.…”

Estrogen Receptor β, but not α, Mediates Estrogen's Effect on Cocaine-Induced Reinstatement of Extinguished Cocaine-Seeking Behavior in Ovariectomized Female Rats

“…Thus, in addition to promoting reinstatement of cocaine-seeking behavior, cocaine may have also caused increased locomotor activity in these animals. The finding that the OVX + EB rats had greater inactive lever responding than OVX + DMSO rats is consistent with several studies that found that the locomotor activity produced by cocaine, at similar bolus doses that were used in the present study, was enhanced by estrogen treatment (eg, Sell et al, 2000Sell et al, , 2002Perrotti et al, 2001;Chin et al, 2002). Interestingly, in contrast to what was found for active lever responding, the effect of EB on inactive lever responding was also found in rats pretreated with PPT, but not those pretreated with DPN.…”

Effects of allopregnanolone on the reinstatement of cocaine-seeking behavior in male and female rats

“…Also, the administration of PROG in estrogen-treated ovariectomized rats decreased stimulantinduced behaviors relative to ovariectomized rats treated with estrogen alone Jackson et al 2006;Larson et al 2005Quinones-Jenab et al 2000). Administering PROG alone had negligible effects on stimulant-induced behavior in ovariectomized female rats (Perrotti et al 2001;Quinones-Jenab et al 2000;Sell et al 2000;Sircar and Kim 1999). A limitation of the present study was that the estrous phase and hormone levels were not controlled for; thus, we could not examine estrogen-ALLO interactions on cocaine seeking.…”