scholarly journals Examining Sex Differences in Conditioned Place Preference or Aversion to Methamphetamine in Adolescent and Adult Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Ellen R. Cullity ◽  
Alexandre A. Guerin ◽  
Christina J. Perry ◽  
Jee Hyun Kim

Adolescence marks a particularly vulnerable period to developing substance use disorders. Human and rodent studies suggest that hypersensitivity to reward may contribute towards such vulnerability when adolescents are exposed to casual drug use. Methamphetamine is a popular illicit substance used by male and female youths. However, age- and sex-specific research in methamphetamine is scarce. The present study therefore aimed to examine potential sex differences in methamphetamine-conditioned place preference in adolescent and adult mice. Mice (n = 16–24/group) were conditioned to methamphetamine (0.1 mg/kg). We observed that regardless of age, females were more hyperactive compared to males. Individually normalized score against baseline preference indicated that on average, adolescents formed stronger preference compared to adults in both sexes. This suggests that adolescents are more sensitive to the rewarding effects of methamphetamine compared to adults. Surprisingly, individual data showed that some mice formed a conditioned place aversion instead of preference, with females less likely to form an aversion compared to males. These results suggest that adolescents may be hypersensitive to methamphetamine’s rewarding effects. In addition, female resistance to the aversive effects of methamphetamine may relate to the sex-specific findings in humans, including quicker transition to regular methamphetamine use observed in females compared to males.

2021 ◽  
Vol 3 ◽  
pp. e24
Author(s):  
Ellen Rose Cullity ◽  
Alexandre Arthur Guérin ◽  
Heather Bronwyn Madsen ◽  
Christina Jennifer Perry ◽  
Jee Hyun Kim

Rodent studies have proposed that adolescent susceptibility to substance use is at least partly due to adolescents experiencing reduced aversive effects of drugs compared to adults. We thus investigated methamphetamine (meth) conditioned place preference/aversion (CPP/CPA) in adolescent and adult mice in both sexes using a high dose of meth (3 mg/kg) or saline as controls. Mice tagged with green-fluorescent protein (GFP) at Drd1a or Drd2 were used so that dopamine receptor 1 (D1) and 2 (D2) expression within the insular cortex (insula) could be quantified. There are sex differences in how the density of D1+ and D2+ cells in the insula changes across adolescence that may be related to drug-seeking behaviors. Immunohistochemistry followed by stereology were used to quantify the density of cells with c-Fos and/or GFP in the insula. Unexpectedly, mice showed huge variability in behaviors including CPA, CPP, or no preference or aversion. Females were less likely to show CPP compared to males, but no age differences in behavior were observed. Conditioning with meth increased the number of D2 + cells co-labelled with c-Fos in adults but not in adolescents. D1:D2 ratio also sex- and age-dependently changed due to meth compared to saline. These findings suggest that reduced aversion to meth is unlikely an explanation for adolescent vulnerability to meth use. Sex- and age-specific expressions of insula D1 and D2 are changed by meth injections, which has implications for subsequent meth use.


Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Łukasz Kurach ◽  
Agnieszka Michalak ◽  
Anna Boguszewska-Czubara ◽  
...  

Abstract Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats. Methods The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. Results Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus. Conclusions Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.


2017 ◽  
Vol 52 (suppl_1) ◽  
pp. i4-i30
Author(s):  
R Camarini ◽  
A.B. Suárez ◽  
L.B. Hoffmann ◽  
A.V. Rueda ◽  
M.B. Rae ◽  
...  

2020 ◽  
Vol 28 (12) ◽  
pp. 1749-1755
Author(s):  
Hashem O. Alsaab ◽  
Ebtehal Altowairqi ◽  
Nada Alzahrani ◽  
Reem Alzahrani ◽  
Fahad S. Alshehri ◽  
...  

1989 ◽  
Vol 16 (2-4) ◽  
pp. 375-383 ◽  
Author(s):  
Rene de Beun ◽  
Nora E. Geerts ◽  
Nanne E. van de Poll ◽  
Jef L. Slangen ◽  
Jan T. M. Vreeburg

2021 ◽  
Vol 15 ◽  
Author(s):  
Prableen K. Singh ◽  
Kabirullah Lutfy

Endogenous opioids have been implicated in cocaine reward. However, the role of each opioid peptide in this regard is unknown. Notably, the role of each peptide in extinction and reinstatement is not fully characterized. Thus, we assessed whether cocaine-induced conditioned place preference (CPP) and its extinction and reinstatement would be altered in the absence of beta-endorphin. We also examined if sex-related differences would exist in these processes. Male and female mice lacking beta-endorphin and their respective controls were tested for baseline place preference on day 1. On day 2, mice were treated with saline/cocaine (15 mg/kg) and confined to the vehicle- or drug-paired chamber for 30 min, respectively. In the afternoon, mice were treated with the alternate treatment and confined to the opposite chamber. Mice were then tested for CPP on day 3. Mice then received additional conditioning on this day as well as on day 4. Mice were then tested for CPP on day 5. Mice then received extinction training on day 9. On day 10, mice were tested for extinction and then reinstatement of CPP following a priming dose of cocaine (7.5 mg/kg). Male and female mice lacking beta-endorphin did not exhibit CPP following single conditioning with cocaine. On the other hand, only male mice lacking beta-endorphin failed to show CPP after repeated conditioning. Nonetheless, reinstatement of CPP was blunted in both male and female mice lacking beta-endorphin compared to controls. The present results suggest that beta-endorphin plays a functional role in cocaine-induced CPP and its reinstatement, and sex-related differences exist in the regulatory action of beta-endorphin on the acquisition but not reinstatement of cocaine CPP.


2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Matthias Alexander Zingg ◽  
Mathias Wolfrum ◽  
Christoph Alexander Rüst ◽  
Thomas Rosemann ◽  
Romuald Lepers ◽  
...  

AbstractPurpose. Recent studies have suggested that the age of peak freestyle swimming speed is reached earlier in life in women than in men. However, no study has investigated the age of peak swimming speed in other swimming styles such as butterfly. The aims of the present study were to investigate the age of peak swimming speed in elite male and female butterfly and freestyle swimmers at the national level (Switzerland) and the sex differences in both the age of peak swimming speed and swimming speed for both swimming styles. Methods. Results of the elite Swiss swimmers between 2006 and 2010 were analysed using one-way analysis of variance. Results. In butterfly, women achieved peak swimming speed at 20-21 years in the 50 m, 100 m and 200 m, whereas men reached their fastest swimming speed in the 50 m at 20-21 years and in both the 100 m and 200 m at 18-19 years. In freestyle, women achieved peak swimming speed at 20-21 years for all distances. Men were the fastest at 22-23 years for both the 100 m and 200 m and at 26-27 years for the 50 m. In the butterfly, the sex difference in swimming speed was highest in the 50 m and lowest in the 200 m (14.1% ± 0.2 in the 50 m, 12.6% ± 1.0 in the 100 m and 8.7% ± 1.8 in the 200 m). Additionally, the sex difference in freestyle swimming speed was highest in the 50 m and lowest in the 200 m (16.2% ± 0.5 in the 50 m, 15.9% ± 0.4 in 100 m and 14.9% ± 1.0 in 200 m). Conclusions. These findings suggest that peak swimming speed was achieved earlier in life in men compared with women for the 100 m and 200 m butterfly distances but not in the 50 m butterfly. In freestyle, peak swimming speed was achieved at younger ages in women compared with men. The sex difference in peak swimming speed was lower in the butterfly than in freestyle.


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