Estrogen and opioids interact to modulate the locomotor response to cocaine in the female rat

Febo, Marcelo; Jiménez‐Rivera, Carlos A.; Segarra, Annabell C.

doi:10.1016/s0006-8993(02)02748-8

Cited by 25 publications

(34 citation statements)

References 77 publications

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“…SILASTIC tubing implants (inner diameter, 1.47 mm; outer diameter, 1.97 mm; 0.23 mm wall thickness) (Dow Corning 508-006; VWR Scientific, Bridgeport, NJ) were prepared according to Febo et al (2002). Briefly, 5-mm-long sections of tubing were sealed on one end with SILASTIC silicone sealant (Dow Corning 732; VWR) and allowed to dry for 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…SILASTIC implants achieve stable levels of plasma hormones that last well over 30 d. The release rate depends on the length and wall thickness of the implant; for a 5-mm-long section with similar dimensions, the release rate has been estimated to be ϳ75-100 pg/ml per 24 h (Dziuk and Cook, 1966;Bridges, 1984). Previously, we have reported total plasma 17-␤-estradiol concentrations of 141.4 Ϯ 17.0 pg/ml (range, 94 -192 pg/ml) 15 d after initial subcutaneous placement in ovariectomized (Ovx) females (Febo et al, 2002). Ovx females with empty implants show nondetectable levels of estrogen (Ͻ3 pg/ml) (Febo et al, 2002).…”

Section: Methodsmentioning

confidence: 99%

“…The current evidence indicates that this sex steroid interacts with many neurotransmitter systems that are also affected by repeated cocaine administration. These include dopamine (Febo et al, 2003), opioid (Febo et al, 2002), serotonin (Chang and Chang, 1999), GABA (Lagrange et al, 1996;, and glutamate (Woolley et al, 1997) systems. The modulatory actions of estrogen extend beyond the mesolimbic dopamine system into brain areas that play crucial roles in behavioral sensitization, such as the hippocampus and prefrontal cortex (Woolley et al, 1997;Shansky et al, 2003;Tang et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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

Febo¹,

Ferris²,

Segarra³

2005

J. Neurosci.

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Febo¹,

Ferris²,

Segarra³

2005

J. Neurosci.

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“…Details of the test arenas and control software are provided in previous publications (Febo et al, 2003(Febo et al, , 2002. Animals were tested 1 week after imaging.…”

Section: Locomotor Activity Measurementsmentioning

confidence: 99%

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

Colon-Perez

Tran

Thompson

et al. 2016

Neuropsychopharmacol

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The abuse of 'bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D 1 /D 2 receptor antagonist cis-flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks involving frontal cortical and striatal regions could contribute to the adverse effects of MDPV.

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“…In contrast, more women than men remain abstinent after treatment (Weiss et al 1997). Thus, women are both more susceptible to cocaine abuse and, paradoxically, more responsive to treatment.A substantial literature supports that estrogens mediate the enhancement of drug seeking observed in females (Febo et al 2002;Larson et al 2007;Segarra et al 2010; Kerstetter and Kippin 2011), but little is known regarding the role of estrogens during treatment. Preclinically, treatment is modeled through extinction learning, which results in the formation of a new inhibitory memory that suppresses drug seeking Torregrossa and Taylor 2012).…”

mentioning

confidence: 99%

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

et al. 2013

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Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17b-estradiol (E 2 ) affects expression and extinction of cocaine seeking in female rats. Using a conditioned place preference (CPP) paradigm, ovariectomized rats were maintained throughout conditioning with 2 d of E 2 treatment followed by 2 d of vehicle treatment, or were injected with E 2 daily. Hormone injections were paired or explicitly unpaired with place conditioning sessions. Expression of a cocaine CPP was of equal magnitude regardless of conditioning protocol, suggesting that E 2 levels during conditioning did not affect subsequent CPP expression. During extinction, daily E 2 administration initially enhanced expression of the cocaine CPP, but resulted in significantly faster extinction compared to controls. Whereas E 2 -treated rats were extinguished within 8 d, vehicle-treated rats maintained CPP expression for more than a month, indicative of perseveration. To determine whether E 2 could rescue extinction in these rats, half were given daily E 2 treatment and half were given vehicle. E 2 -treated rats showed rapid extinction, whereas vehicle-treated rats continued to perseverate. These data demonstrate for the first time that E 2 is necessary for extinction of cocaine seeking in female rats, and that it promotes rapid extinction when administered daily. Clinically, these findings suggest that monitoring and maintaining optimal E 2 levels during exposure therapy would facilitate therapeutic interventions for female cocaine addicts.Gonadal hormones render women more susceptible than men to developing compulsive patterns of psychostimulant use. Natural fluctuations in levels of the primary ovarian hormones, estrogens and progesterone, account for this increased abuse liability. Higher levels of estrogens, and lower levels of progesterone, are associated with greater sensitivity to the euphorigenic properties of cocaine in women (Evans 2007). This increased sensitivity may contribute to why women, compared with men, start using cocaine regularly at a younger age (Chen and Kandel 2002), transition from use to abuse more quickly (McCance-Katz et al. 1999), experience greater craving in response to drug-associated cues (Robbins et al. 1999) and stress (Potenza et al. 2012;Waldrop et al. 2012), and exhibit more severe drug-seeking behavior upon relapse (Gallop et al. 2007). In contrast, more women than men remain abstinent after treatment (Weiss et al. 1997). Thus, women are both more susceptible to cocaine abuse and, paradoxically, more responsive to treatment.A substantial literature supports that estrogens mediate the enhancement of drug seeking observed in females (Febo et al. 2002;Larson et al. 2007;Segarra et al. 2010; Kerstetter and Kippin 2011), but little is known regarding the role of estrogens during treatment. Preclinically, treatment is modeled through ext...

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Estrogen and opioids interact to modulate the locomotor response to cocaine in the female rat

Cited by 25 publications

References 77 publications

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

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

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

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