scholarly journals Estradiol as a Mechanism for Sex Differences in the Development of an Addicted Phenotype following Extended Access Cocaine Self-Administration

2013 ◽  
Vol 38 (9) ◽  
pp. 1698-1705 ◽  
Author(s):  
Carolina P Ramôa ◽  
Susan E Doyle ◽  
Diana W Naim ◽  
Wendy J Lynch
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Akhil Sharma ◽  
Arman Harutyunyan ◽  
Bernard L. Schneider ◽  
Anna Moszczynska

AbstractThere is no FDA-approved medication for methamphetamine (METH) use disorder. New therapeutic approaches are needed, especially for people who use METH heavily and are at high risk for overdose. This study used genetically engineered rats to evaluate PARKIN as a potential target for METH use disorder. PARKIN knockout, PARKIN-overexpressing, and wild-type young adult male Long Evans rats were trained to self-administer high doses of METH using an extended-access METH self-administration paradigm. Reinforcing/rewarding properties of METH were assessed by quantifying drug-taking behavior and time spent in a METH-paired environment. PARKIN knockout rats self-administered more METH and spent more time in the METH-paired environment than wild-type rats. Wild-type rats overexpressing PARKIN self-administered less METH and spent less time in the METH-paired environment. PARKIN knockout rats overexpressing PARKIN self-administered less METH during the first half of drug self-administration days than PARKIN-deficient rats. The results indicate that rats with PARKIN excess or PARKIN deficit are useful models for studying neural substrates underlying “resilience” or vulnerability to METH use disorder and identify PARKIN as a novel potential drug target to treat heavy use of METH.


2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

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.


2011 ◽  
Vol 17 (2) ◽  
pp. 300-308 ◽  
Author(s):  
Eric P. Zorrilla ◽  
Sunmee Wee ◽  
Yu Zhao ◽  
Sheila Specio ◽  
Benjamin Boutrel ◽  
...  

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Robert Seaman ◽  
Agnieszka Sulima ◽  
Kenner Rice ◽  
Gregory Collins

2005 ◽  
Vol 180 (3) ◽  
pp. 414-426 ◽  
Author(s):  
Marilyn E. Carroll ◽  
David K. Batulis ◽  
Kerry L. Landry ◽  
Andrew D. Morgan

2002 ◽  
Vol 161 (3) ◽  
pp. 304-313 ◽  
Author(s):  
Marilyn Carroll ◽  
Andrew Morgan ◽  
Wendy Lynch ◽  
Una Campbell ◽  
Nancy Dess

2011 ◽  
Vol 17 (6) ◽  
pp. 964-976 ◽  
Author(s):  
Magalie Lenoir ◽  
Karyn Guillem ◽  
George F. Koob ◽  
Serge H. Ahmed

2019 ◽  
Vol 22 (2) ◽  
pp. 204-212 ◽  
Author(s):  
Jillian J Weeks ◽  
Laura E Rupprecht ◽  
Anthony A Grace ◽  
Eric C Donny ◽  
Alan F Sved

Abstract Introduction Patients with schizophrenia (SCZ) smoke at a rate of 4–5 times higher than the general population, contributing to negative health consequences in this group. One possible explanation for this increased smoking is that individuals with SCZ find nicotine (NIC) more reinforcing. However, data supporting this possibility are limited. Methods The present experiments examined self-administration of NIC, alone or in combination with other reinforcers, across a range of doses in the methylazoxymethanol acetate (MAM) rodent model of SCZ. Results MAM and control animals did not differ in NIC self-administration across a range of doses and schedules of reinforcement, in both standard 1-hour self-administration sessions and 23-hour extended access sessions. However, MAM animals responded less for sucrose or reinforcing visual stimuli alone or when paired with NIC. Conclusions To the extent that MAM-treated rats are a valid model of SCZ, these results suggest that increased NIC reinforcement does not account for increased smoking in SCZ patients. Implications This study is the first to utilize nicotine self-administration, the gold standard for studying nicotine reinforcement, in the methylazoxymethanol acetate model of schizophrenia, which is arguably the most comprehensive animal model of the disease currently available. Our assessment found no evidence of increased nicotine reinforcement in methylazoxymethanol acetate animals, suggesting that increased reinforcement may not perpetuate increased smoking in schizophrenia patients.


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