scholarly journals The effects of ceftriaxone on cue-primed reinstatement of cocaine-seeking in male and female rats: estrous cycle effects on behavior and protein expression in the nucleus accumbens

2017 ◽  
Vol 235 (3) ◽  
pp. 837-848 ◽  
Author(s):  
Allison R. Bechard ◽  
Peter U. Hamor ◽  
Marek Schwendt ◽  
Lori A. Knackstedt
Keyword(s):  
Nucleus Accumbens ◽  
Protein Expression ◽  
Estrous Cycle ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cocaine Seeking

scholarly journals Metformin in nucleus accumbens core reduces cue-induced cocaine seeking in male and female rats

2021 ◽  
Author(s):  
Amy Chan ◽  
Alexis Willard ◽  
Sarah Mulloy ◽  
Noor Ibrahim ◽  
Allegra Sciaccotta ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Female Rats ◽  
Therapeutic Effects ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cocaine Seeking ◽  
Ampk Activity ◽  
Accumbens Core

This study investigated the potential therapeutic effects of the FDA-approved drug metformin on cue-induced reinstatement of cocaine seeking. Metformin (dimethyl-biguanide) is a first-line treatment for type II diabetes that, among other mechanisms, is involved in the activation of adenosine monophosphate activated protein kinase (AMPK). Cocaine self-administration and extinction is associated with decreased levels of phosphorylated AMPK within the nucleus accumbens core (NAcore). Previously it was shown that increasing AMPK activity in the NAcore decreased cue-induced reinstatement of cocaine seeking. Decreasing AMPK activity produced the opposite effect. The goal of the present study was to determine if metformin in the NAcore reduces cue-induced cocaine seeking in adult male and female Sprague Dawley rats. Rats were trained to self-administer cocaine followed by extinction prior to cue-induced reinstatement trials. Metformin microinjected in the NAcore attenuated cue-induced reinstatement in male and female rats. Importantly, metformin's effects on cocaine seeking were not due to a general depression of spontaneous locomotor activity. In female rats, metformin's effects did generalize to a reduction in cue-induced reinstatement of sucrose seeking. These data support a potential role for metformin as a pharmacotherapy for cocaine use disorder, but warrant caution given the potential for metformin's effects to generalize to a natural reward in female rats.

scholarly journals Ceftriaxone and mGlu2/3 interactions in the nucleus accumbens core affect the reinstatement of cocaine-seeking in male and female rats

2020 ◽  
Vol 237 (7) ◽  
pp. 2007-2018 ◽  
Author(s):  
Carly N. Logan ◽  
Allison R. Bechard ◽  
Peter U. Hamor ◽  
Lizhen Wu ◽  
Marek Schwendt ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Female Rats ◽  
Nucleus Accumbens Core ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cocaine Seeking ◽  
Core Affect ◽  
Accumbens Core

scholarly journals Ceftriaxone and mGlu2/3 interactions in the nucleus accumbens core affect the reinstatement of cocaine-seeking in male and female rats

2020 ◽  
Author(s):  
Carly N. Logan ◽  
Allison R. Bechard ◽  
Peter U. Hamor ◽  
Lizhen Wu ◽  
Marek Schwendt ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Surface Expression ◽  
Receptor Expression ◽  
Female Rats ◽  
Beta Lactam ◽  
Nucleus Accumbens Core ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cocaine Seeking ◽  
Accumbens Core

AbstractRationaleThe beta-lactam antibiotic ceftriaxone reliably attenuates the reinstatement of cocaine-seeking. While the restoration of nucleus accumbens core (NA core) GLT-1 expression is necessary for ceftriaxone to attenuate reinstatement, AAV-mediated GLT-1 overexpression is not sufficient to attenuate reinstatement and does not prevent glutamate efflux during reinstatement.AimsHere, we test the hypothesis that ceftriaxone attenuates reinstatement through interactions with glutamate autoreceptors mGlu2 and mGlu3 in the NA core.MethodsMale and female rats self-administered cocaine for 12 days followed by 2-3 weeks of extinction training. During the last 6-10 days of extinction, rats received ceftriaxone (200 mg/kg IP) or vehicle. In experiment 1, rats were killed, and NA core tissue was biotinylated for assessment of total and surface expression of mGlu2 and mGlu3 via western blotting. In experiment 2, we tested the hypothesis that mGlu2/3 signaling is necessary for ceftriaxone to attenuate cue- and cocaine-primed reinstatement by administering bilateral intra-NA core infusion of mGlu2/3 antagonist LY341495 or vehicle immediately prior to reinstatement testing.ResultsmGlu2 expression was reduced by cocaine and restored by ceftriaxone. There were no effects of cocaine or ceftriaxone on mGlu3 expression. We observed no effects of estrus on expression of either protein. The antagonism of mGlu2/3 in the NA core during both cue- and cocaine-primed reinstatement tests prevented ceftriaxone from attenuating reinstatement.ConclusionsThese results indicate that ceftriaxone’s effects depend on mGlu2/3 function and possibly mGlu2 receptor expression. Future work will test this hypothesis by manipulating mGlu2 expression in pathways that project to the NA core.

scholarly journals Allopregnanolone Decreases Evoked Dopamine Release Differently in Rats by Sex and Estrous Stage

2021 ◽  
Vol 11 ◽  
Author(s):  
Ana Paula S. Dornellas ◽  
Giovana C. Macedo ◽  
Minna H. McFarland ◽  
Alexander Gómez-A ◽  
Todd K. O’Buckley ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Estrous Cycle ◽  
Dopamine Release ◽  
Female Rats ◽  
Male Rats ◽  
Therapeutic Effects ◽  
Mesolimbic Dopamine ◽  
Male And Female ◽  
Male And Female Rats ◽  
Dopamine Transmission

Mesolimbic dopamine transmission is dysregulated in multiple psychiatric disorders, including addiction. Previous studies found that the endogenous GABAergic steroid (3α,5α)-3-hydroxy-5-pregnan-20-one (allopregnanolone) modulates dopamine levels in the nucleus accumbens and prefrontal cortex. As allopregnanolone is a potent positive allosteric modulator of GABAA receptors, and GABAA receptors can regulate dopamine release, we hypothesized that allopregnanolone would reduce phasic fluctuations in mesolimbic dopamine release that are important in learning and reward processing. We used fast-scan cyclic voltammetry in anesthetized female and male rats to measure dopamine release in the nucleus accumbens evoked by electrical stimulation of the ventral tegmental area, before and after administration of allopregnanolone. Allopregnanolone (7.5–25 mg/kg, IP) reduced evoked dopamine release in both male and female rats, compared to β-cyclodextrin vehicle. In males, all doses of allopregnanolone decreased dopamine transmission, with stronger effects at 15 and 25 mg/kg allopregnanolone. In females, 15 and 25 mg/kg allopregnanolone reduced dopamine release, while 7.5 mg/kg allopregnanolone was no different from vehicle. Since allopregnanolone is derived from progesterone, we hypothesized that high endogenous progesterone levels would result in lower sensitivity to allopregnanolone. Consistent with this, females in proestrus (high progesterone levels) were less responsive to allopregnanolone than females in other estrous cycle stages. Furthermore, 30 mg/kg progesterone reduced evoked dopamine release in males, similar to allopregnanolone. Our findings confirm that allopregnanolone reduces evoked dopamine release in both male and female rats. Moreover, sex and the estrous cycle modulated this effect of allopregnanolone. These results extend our knowledge about the pharmacological effects of neurosteroids on dopamine transmission, which may contribute to their therapeutic effects.

scholarly journals Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Fixed Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Self Administration ◽  
Male And Female ◽  
Orexin Receptors ◽  
Male And Female Rats

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.

scholarly journals Attenuated cocaine-seeking after oxytocin administration in male and female rats

2018 ◽  
Vol 235 (7) ◽  
pp. 2051-2063 ◽  
Author(s):  
Amy S. Kohtz ◽  
Belle Lin ◽  
Michael E. Smith ◽  
Gary Aston-Jones
Keyword(s):  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cocaine Seeking

scholarly journals Gender Differences in the Effect of Prenatal Methamphetamine Exposure and Challenge Dose of Other Drugs on Behavior of Adult Rats

2013 ◽  
pp. S99-S108 ◽  
Author(s):  
R. ŠLAMBEROVÁ ◽  
E. MACÚCHOVÁ ◽  
K. NOHEJLOVÁ-DEYKUN ◽  
B. SCHUTOVÁ ◽  
L. HRUBÁ ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Adult Male ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Male Rats ◽  
Prenatally Exposed ◽  
Challenge Dose ◽  
Adult Rats ◽  
Male And Female ◽  
Male And Female Rats

The aim of the present study was to compare the response to acute application of several drugs in adult male and female rats prenatally exposed to methamphetamine (MA). Spontaneous locomotor activity and exploratory behavior of adult male and female rats prenatally exposed to MA (5 mg/kg) or saline were tested in a Laboras apparatus (Metris B.V., Netherlands) for 1 h. Challenge dose of the examined drug [amphetamine – 5 mg/kg; cocaine – 5mg/kg; MDMA (3,4-methylenedioxymethamphetamine) – 5 mg/kg; morphine – 5 mg/kg; THC (delta9-tetrahydrocannabinol) – 2 mg/kg] or saline was injected prior to testing. Our data demonstrate that prenatal MA exposure did not affect behavior in male rats with cocaine or morphine treatment, but increased locomotion and exploration in females. Application of amphetamine and MDMA in adulthood increased activity in both sexes, while cocaine and THC only in female rats. Morphine, on the other hand, decreased the activity in the Laboras test in both sexes. As far as sex and estrous cycle is concerned, the present study shows that males were generally less active than females and also females in proestrus-estrus phase of the estrous cycle were more active than females in diestrus. In conclusion, the present study shows that the prenatal MA exposure does not induce general sensitization but affects the sensitivity to drugs dependently to mechanism of drug action and with respect to gonadal hormones.

Sign in / Sign up

Export Citation Format

Share Document