Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour

Abstract BackgroundEstradiol potentiates drug-taking behaviors, including motivation to self-administer cocaine and reinstatement of drug-seeking after extinction in females, but not males. The dorsolateral stratum (DLS) is a region of the brain implicated in mediating drug-seeking behaviors and more specifically, is a target brain area to study how estradiol regulates these behaviors. The estradiol receptors α, β, and G-protein coupled estradiol receptor 1 (GPER1) are all present in the DLS. In this study the effects of activating GPER1 in the DLS on drug-seeking are investigated. MethodsGonad-intact male and female rats were trained to self-administer cocaine (0.4 mg/kg/inf) on an fixed-ratio 1 schedule of reinforcement. For four weeks, animals underwent testing on a progressive ratio schedule of reinforcement to determine their motivation to attain cocaine. Halfway through progressive ratio testing, a selective agonist targeting GPER1 (G1) was administered intra-DLS to determine the contribution of GPER1 activation on motivation for cocaine. The effects of intra-GPER1 activation on drug-induced reinstatement after extinction was subsequently determined. ResultsActivation of GPER1, via G1 administration intra-DLS potentiated females’ motivation to self-administer cocaine. There was no effect of prior G1 treatment on extinction of cocaine-taking in females, however, G1 treatment resulted in greater drug-induced reinstatement (10 mg/kg cocaine, i.p.). There were no effects of intra-DLS GPER1 activation observed on motivation for cocaine or cocaine-induced reinstatement of responding in males. Conclusions These results support the conclusion that activation of GPER1 in the DLS enhances cocaine seeking behaviors for female, but not male rats.

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Estrogens are Necessary for Expression of Cocaine Seeking in Male Rats

The FASEB Journal ◽

10.1096/fasebj.2018.32.1_supplement.820.6 ◽

2018 ◽

Vol 32 (S1) ◽

Author(s):

Daniel Alejandro Acevedo ◽

John Alvarado ◽

Lilith Torres ◽

Bermary Santos‐Vera ◽

Devin Mueller

Keyword(s):

Male Rats ◽

Cocaine Seeking

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Administration of orexin A in the posterior paraventricular nucleus of the thalamus promotes cocaine-seeking behavior and is associated with hypothalamic activation

10.1101/185538 ◽

2017 ◽

Author(s):

Alessandra Matzeu ◽

Rémi Martin-Fardon

Keyword(s):

Paraventricular Nucleus ◽

Priming Effect ◽

Cocaine Dependence ◽

Activation Pattern ◽

Neuronal Activation ◽

Drug Seeking ◽

Protracted Abstinence ◽

Cocaine Seeking ◽

Seeking Behavior ◽

History Of

ABSTRACTHypothalamic orexin (Orx) neurons that project to the paraventricular nucleus of the thalamus (PVT) have received growing interest because of their role in drug-seeking behavior. When injected in the posterior PVT (pPVT), OrxA reinstated extinguished cocaine-seeking behavior in rats that had long access (LgA) to cocaine for 6 h/day after an intermediate period of abstinence (I-Abst, 2-3 weeks). Considering the long-lasting nature of drug-seeking behavior and that the PVT sends projections to the hypothalamus, the present study examined whether (i) OrxA’s priming effect is preserved after a period of protracted abstinence (P-Abst, 4-5 weeks) in LgA rats and (ii) the neural activation pattern (i.e., Fos+ and Fos+/Orx+ cells) in the lateral hypothalamus (LH), dorsomedial hypothalamus (DMH), and perifornical area (PFA) following intra-pPVT OrxA administration that may explain OrxA-induced reinstatement in LgA animals. As reported previously, OrxA administration in the pPVT triggered cocaine-seeking behavior after I-Abst. With P-Abst, the priming effect of OrxA was absent. An intra-pPVT injection of OrxA produced a strong increase in neuronal activation (i.e., Fos expression) in the LH/DMH/PFA at I-Abst but not at P-Abst. The analysis of the activation (Fos+) of Orx neurons (Orx+) revealed an increase in Fos+/Orx+ expression in the LH/DMH/PFA at I-Abst only, thus paralleling the behavioral data. These data indicate that shortly after abstinence, PVT↔LH/DMH/PFA connections are strongly recruited in animals with a history of cocaine dependence. The lack of effect at P-Abst suggests that the function of Orx receptors and connectivity of the PVT↔LH/DMH/PFA circuit undergo significant neuroadaptations following P-Abst.SIGNIFICANCE STATEMENTA better understanding of the pathophysiological changes associated with cocaine addiction is needed to develop efficient pharmacotherapies. The paraventricular nucleus of the thalamus (PVT) and orexin (Orx) transmission within the PVT have been implicated in maladaptive (compulsive) behavior that is characteristic of drug addiction. The present study shows OrxA injections in the posterior PVT reinstates cocaine-seeking behavior in animals with a history of cocaine dependence, and this effect disappears after protracted abstinence, paralleled by the neuronal activation pattern in the hypothalamus. In subjects with a history of cocaine dependence, the function of Orx receptors and connectivity of the PVT↔ LH/DMH/PFA circuit undergo significant neuroadaptations.

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Effect of Amphetamine on Adult Male and Female Rats Prenatally Exposed to Methamphetamine

Prague Medical Report ◽

10.14712/23362936.2014.5 ◽

2014 ◽

Vol 115 (1-2) ◽

pp. 43-59 ◽

Cited By ~ 5

Author(s):

Romana Šlamberová ◽

Eva Macúchová ◽

Kateryna Nohejlová ◽

Andrea Štofková ◽

Jana Jurčovičová

Keyword(s):

Spatial Memory ◽

Adult Male ◽

Drug Exposure ◽

Prenatal Drug Exposure ◽

Female Rats ◽

Male Rats ◽

Daily Injection ◽

Drug Seeking ◽

Male And Female ◽

Male And Female Rats

The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), active drug-seeking behaviour in conditioned place preference test (CPP), spatial memory in the Morris water maze (MWM), and levels of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled) regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing) only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

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ARC and BDNF expression after cocaine self-administration or cue-induced reinstatement of cocaine seeking in adolescent and adult male rats

Addiction Biology ◽

10.1111/adb.12689 ◽

2018 ◽

Vol 23 (6) ◽

pp. 1233-1241 ◽

Cited By ~ 4

Author(s):

Chen Li ◽

Alexandria C. White ◽

Terri Schochet ◽

Jacqueline F. McGinty ◽

Kyle J. Frantz

Keyword(s):

Adult Male ◽

Male Rats ◽

Self Administration ◽

Bdnf Expression ◽

Cocaine Seeking

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Susceptibility of Drug-seeking and Taking Behaviors Increases through Dysregulation of Copper and Zinc and Impaired Prefrontal Function in Addiction Period in Male Rats

International Journal of Biochemistry Research & Review ◽

10.9734/ijbcrr/2016/28542 ◽

2016 ◽

Vol 13 (3) ◽

pp. 1-8

Author(s):

Hamidreza Famitafreshi ◽

Morteza Karimian ◽

Masoud Afshari

Keyword(s):

Male Rats ◽

Drug Seeking ◽

Copper And Zinc ◽

Prefrontal Function

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Effects of an acute cannabidiol treatment on cocaine self-administration and cue-induced cocaine seeking in male rats

Journal of Psychopharmacology ◽

10.1177/0269881116667706 ◽

2016 ◽

Vol 31 (1) ◽

pp. 96-104 ◽

Cited By ~ 19

Author(s):

Ashraf Mahmud ◽

Stephanie Gallant ◽

Firas Sedki ◽

Tracey D’Cunha ◽

Uri Shalev

Keyword(s):

Elevated Plus Maze ◽

Anxiolytic Effect ◽

Progressive Ratio ◽

Male Rats ◽

Self Administration ◽

Schedule Of Reinforcement ◽

Cocaine Seeking ◽

Therapeutic Value ◽

Plus Maze ◽

Wide Range

Cannabidiol is a non-psychoactive compound that is the second most abundant component of cannabis. It has been shown to have a potential therapeutic value for a wide range of disorders, including anxiety, psychosis, and depression. Recently, it was suggested that cannabidiol might be a potential treatment for heroin craving and relapse. Here we investigated the effects of an acute treatment with cannabidiol on cocaine self-administration and cue-induced cocaine seeking in rats. Rats were trained to press a lever to self-administer cocaine (0.5 mg/kg/infusion), first under a fixed interval 20 s (FI-20 s) and then under a progressive ratio (PR) schedule of reinforcement. Cocaine self-administration under a PR schedule of reinforcement was not attenuated by cannabidiol injections (5.0 mg/kg and 10.0 mg/kg; i.p.) when tested 30 min and 24 h after treatment. Cannabidiol treatment (5.0 mg/kg or 10.0 mg/kg) also did not attenuate cue-induced cocaine seeking in rats after a withdrawal period of 14 days. In contrast, treatment with cannabidiol (10.0 mg/kg; i.p.) resulted in a statistically significant anxiolytic effect in the elevated plus-maze. Our findings suggest that, under the conditions described here, an acute cannabidiol treatment has a minimal effect on a rat model of cocaine intake and relapse.

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