scholarly journals Insular cortex dopamine 1 and 2 receptors in methamphetamine conditioned place preference and aversion: Age and sex differences

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.

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.


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 ◽  
...  

Blood ◽  
2004 ◽  
Vol 103 (10) ◽  
pp. 3615-3623 ◽  
Author(s):  
Jonathan Back ◽  
Andrée Dierich ◽  
Corinne Bronn ◽  
Philippe Kastner ◽  
Susan Chan

Abstract PU.1 is a hematopoietic-specific transcriptional activator that is absolutely required for the differentiation of B lymphocytes and myeloid-lineage cells. Although PU.1 is also expressed by early erythroid progenitor cells, its role in erythropoiesis, if any, is unknown. To investigate the relevance of PU.1 in erythropoiesis, we produced a line of PU.1-deficient mice carrying a green fluorescent protein reporter at this locus. We report here that PU.1 is tightly regulated during differentiation—it is expressed at low levels in erythroid progenitor cells and down-regulated upon terminal differentiation. Strikingly, PU.1-deficient fetal erythroid progenitors lose their self-renewal capacity and undergo proliferation arrest, premature differentiation, and apoptosis. In adult mice lacking one PU.1 allele, similar defects are detected following stress-induced erythropoiesis. These studies identify PU.1 as a novel and critical regulator of erythropoiesis and highlight the versatility of this transcription factor in promoting or preventing differentiation depending on the hematopoietic lineage.


2011 ◽  
Vol 300 (2) ◽  
pp. G334-G344 ◽  
Author(s):  
Shigeo Takaishi ◽  
Wataru Shibata ◽  
Hiroyuki Tomita ◽  
Guangchun Jin ◽  
Xiangdong Yang ◽  
...  

Gastrin is secreted from a subset of neuroendocrine cells residing in the gastric antrum known as G cells, but low levels are also expressed in fetal pancreas and intestine and in many solid malignancies. Although past studies have suggested that antral gastrin is transcriptionally regulated by inflammation, gastric pH, somatostatin, and neoplastic transformation, the transcriptional regulation of gastrin has not previously been demonstrated in vivo. Here, we describe the creation of an enhanced green fluorescent protein reporter (mGAS-EGFP) mouse using a bacterial artificial chromosome that contains the entire mouse gastrin gene. Three founder lines expressed GFP signals in the gastric antrum and the transitional zone to the corpus. In addition, GFP(+) cells could be detected in the fetal pancreatic islets and small intestinal villi, but not in these organs of the adult mice. The administration of acid-suppressive reagents such as proton pump inhibitor omeprazole and gastrin/CCK-2 receptor antagonist YF476 significantly increased GFP signal intensity and GFP(+) cell numbers in the antrum, whereas these parameters were decreased by overnight fasting, octreotide (long-lasting somatostatin ortholog) infusion, and Helicobacter felis infection. GFP(+) cells were also detected in the anterior lobe of the pituitary gland and importantly in the colonic tumor cells induced by administration with azoxymethane and dextran sulfate sodium salt. This transgenic mouse provides a useful tool to study the regulation of mouse gastrin gene in vivo, thus contributing to our understanding of the mechanisms involved in transcriptional control of the gastrin gene.


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

Development ◽  
2000 ◽  
Vol 127 (16) ◽  
pp. 3467-3474 ◽  
Author(s):  
M.A. Ciemerych ◽  
D. Mesnard ◽  
M. Zernicka-Goetz

Recent studies suggest early (preimplantation) events might be important in the development of polarity in mammalian embryos. We report here lineage tracing experiments with green fluorescent protein showing that cells located either near to or opposite the polar body at the 8-cell stage of the mouse embryo retain their same relative positions in the blastocyst. Thus they come to lie on either end of an axis of symmetry of the blastocyst that has recently been shown to correlate with the anterior-posterior axis of the postimplantation embryo (see R. J. Weber, R. A. Pedersen, F. Wianny, M. J. Evans and M. Zernicka-Goetz (1999). Development 126, 5591–5598). The embryonic axes of the mouse can therefore be related to the position of the polar body at the 8-cell stage, and by implication, to the animal-vegetal axis of the zygote. However, we also show that chimeric embryos constructed from 2-cell stage blastomeres from which the animal or the vegetal poles have been removed can develop into normal blastocysts and become fertile adult mice. This is also true of chimeras composed of animal or vegetal pole cells derived through normal cleavage to the 8-cell stage. We discuss that although polarity of the postimplantation embryo can be traced back to the 8-cell stage and in turn to the organisation of the egg, it is not absolutely fixed by this time.


Sign in / Sign up

Export Citation Format

Share Document