Estrogen Influences Cocaine-Induced Blood Oxygen Level-Dependent Signal Changes in Female Rats

Abstract

We investigated the effect of estrogen on cocaine-induced brain activity using blood oxygen level-dependent (BOLD) magnetic resonance imaging. Ovariectomized (Ovx) rats without estrogen and Ovx rats with estrogen (OvxϩE) were given a single saline or cocaine injection (15 mg/kg, i.p.) for 5 d. After 7 d of withdrawal from injections, rats were challenged with cocaine during functional imaging. Acute cocaine administration produced positive BOLD activation in the prefrontal cortex, nucleus accumbens, striatum, ventral tegmental area, and hippocampus, among other brain regions. Positive BOLD signal changes were lower in OvxϩE than in Ovx rats. With repeated cocaine administration, OvxϩE rats showed enhanced BOLD signal changes in the nucleus accumbens, ventral tegmental area, and hippocampus compared with acutely treated animals. Our results indicate that estrogen influences the effects of acute and repeated cocaine administration on BOLD signal changes. The data suggest that in females with estrogen, cocaine-induced neuronal activity is enhanced after repeated cocaine administration. It is possible that the actions of estrogen within the aforementioned brain regions potentiate the behavioral response to cocaine observed in female rats.

Critical period for dopaminergic neuroprotection by hormonal replacement in menopausal rats

“…Implants were air dried and incubated in sterile saline for at least 12e16 hours to allow the initial surge of high-estradiol levels to be released before use. It has been observed that such implants achieve stable levels of plasma estradiol over 30 days, with a release rate of 75e100 pg/mL per 24 hours (see Febo et al, 2005), as confirmed in our previous studies (Rodriguez-Perez et al, 2010. However, stable levels of E2 have also been found to persist for only 7e24 days (Mannino et al, 2005).…”

“…Rats were bilaterally ovariectomized through a dorsal incision and simultaneously (group B) or 6 weeks (group C) or 20 weeks (group D) later received Silastic implants (inserted subcutaneously) in the midscapular region (Dziuk and Cook, 1966;Febo et al, 2005). Silastic implants were prepared with Silastic tubing (1.47 mm inner diameter  1.95 mm outer diameter, Dow Corning 508-006; VWR Scientific, Bridgeport, NJ), as described by Febo et al (2005).…”

“…Silastic implants were prepared with Silastic tubing (1.47 mm inner diameter  1.95 mm outer diameter, Dow Corning 508-006; VWR Scientific, Bridgeport, NJ), as described by Febo et al (2005). Briefly, 5-mm-long sections of tubing were sealed at one end with Silastic silicone sealant (Dow Corning 732; VWR) and left to dry for 30 minutes.…”

U-69593, a kappa opioid receptor agonist, decreases cocaine-induced behavioral sensitization in female rats.

“…Recent data with fMRI demonstrate that estradioltreated female rats sensitized to cocaine show enhanced BOLD activity in brain areas of the reward pathway (Febo et al, 2005), suggesting that estradiol alters the activity of neurotransmitter and/or neuropeptide systems of the reward pathway, which may enhance the behavioral response to cocaine.…”

BOLD fMRI in awake prairie voles: A platform for translational social and affective neuroscience

“…Functional imaging of the brain in awake rodents has proven its utility since its inception nearly two decades ago (Lahti et al, 1998), and has elevated our understanding in a variety of scientific disciplines, including absence seizures (Tenney et al, 2004), maternal care (Febo and Ferris, 2007; Ferris et al, 2005), pain (Yee et al, 2015), reward (Kulkarni et al, 2012), neurodegenerative diseases (Ferris et al, 2014), and drugs of abuse (Febo et al, 2005, 2004; Febo and Ferris, 2007; Madularu et al, 2015). The utility of functional imaging in rodents is largely translational.…”