Abstract:Although best known as a selective estrogen receptor modulator (SERM), tamoxifen is a drug with a wide range of activities. Tamoxifen has demonstrated some efficacy has a therapeutic for bipolar mania and is believed to exert these effects through inhibition of protein kinase C (PKC). As the symptoms of amphetamine treatment in rodents are believed to mimic the symptoms of a manic episode, many of the preclinical studies for this indication have demonstrated that tamoxifen inhibits amphetamine action. The amph… Show more
“…Dopamine release within the NAc is integral to the rewarding and addictive properties of cocaine, and sex differences in the cocaine‐induced dopamine release are likely to contribute to the greater vulnerability to addictive behaviours in females. As oestradiol is known to regulate the dopamine response to drugs of abuse in females, anti‐oestradiol treatments have been proposed as a possible therapeutic approach to treatment of stimulant abuse (Mikelman et al ., ). However, the significant side effects associated with these drugs, particularly side effects mediated by actions at ERα, are a barrier to their widespread use.…”
Background and Purpose
Females are more sensitive than males to both the acute and prolonged effects of psychomotor stimulants. In females, this is regulated by oestradiol, which enhances dopamine release in the dorsal striatum. In this study, we tested the acute effect of oestradiol on dopamine release in the nucleus accumbens (NAc) shell after cocaine administration and investigated which oestradiol receptors (ERs) contribute to sex differences in the response to cocaine.
Experimental Approach
The ability of oestradiol benzoate (EB) to acutely modulate the effect of cocaine on phasic dopamine release in the NAc shell was measured by fast‐scan cyclic voltammetry in anaesthetized male and female rats. The roles of ER subtypes, ERα and ERβ, was determined with selective agonists.
Key Results
EB acutely enhanced the effect of cocaine on stimulated dopamine release from the NAc shell in females but not in male rats only at levels of stimulation expected to optimally saturate dopamine transporters. Enhanced dopamine release after cocaine administration was also observed in females after selective activation of ERβ but not ERα. EB attenuated the effect of cocaine on NAc shell dopamine reuptake in males but not in females.
Conclusions and Implications
Oestradiol acutely and rapidly regulates dopamine release in females and dopamine reuptake in males. In females, oestradiol rapidly enhances the effect of cocaine on dopamine release, likely via activation of ERβ. The effect of oestradiol in males is not seen with selective receptor subtype activation, a topic deserving of further study.
LINKED ARTICLES
This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc
“…Dopamine release within the NAc is integral to the rewarding and addictive properties of cocaine, and sex differences in the cocaine‐induced dopamine release are likely to contribute to the greater vulnerability to addictive behaviours in females. As oestradiol is known to regulate the dopamine response to drugs of abuse in females, anti‐oestradiol treatments have been proposed as a possible therapeutic approach to treatment of stimulant abuse (Mikelman et al ., ). However, the significant side effects associated with these drugs, particularly side effects mediated by actions at ERα, are a barrier to their widespread use.…”
Background and Purpose
Females are more sensitive than males to both the acute and prolonged effects of psychomotor stimulants. In females, this is regulated by oestradiol, which enhances dopamine release in the dorsal striatum. In this study, we tested the acute effect of oestradiol on dopamine release in the nucleus accumbens (NAc) shell after cocaine administration and investigated which oestradiol receptors (ERs) contribute to sex differences in the response to cocaine.
Experimental Approach
The ability of oestradiol benzoate (EB) to acutely modulate the effect of cocaine on phasic dopamine release in the NAc shell was measured by fast‐scan cyclic voltammetry in anaesthetized male and female rats. The roles of ER subtypes, ERα and ERβ, was determined with selective agonists.
Key Results
EB acutely enhanced the effect of cocaine on stimulated dopamine release from the NAc shell in females but not in male rats only at levels of stimulation expected to optimally saturate dopamine transporters. Enhanced dopamine release after cocaine administration was also observed in females after selective activation of ERβ but not ERα. EB attenuated the effect of cocaine on NAc shell dopamine reuptake in males but not in females.
Conclusions and Implications
Oestradiol acutely and rapidly regulates dopamine release in females and dopamine reuptake in males. In females, oestradiol rapidly enhances the effect of cocaine on dopamine release, likely via activation of ERβ. The effect of oestradiol in males is not seen with selective receptor subtype activation, a topic deserving of further study.
LINKED ARTICLES
This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc
“…Tamoxifen, the first drug approved for estrogen positive breast cancer treatment, has resulted in a tremendous increase in the survival rate among breast cancer patients [ 3 ]. However, despite the prominent advantages of tamoxifen, the risk of developing uterine cancer and thromboembolic events are considered major limitations, alongside several side effects such as the alteration of menstruation [ 4 , 5 , 6 ].…”
Purpose: The aim of this work is to optimize a polyethylene glycolated (PEGylated) polymer–lipid hybrid nanoparticulate system for the delivery of anastrozole (ANS) to enhance its biopharmaceutical attributes and overall efficacy. Methods: ANS loaded PEGylated polymer–lipid hybrid nanoparticles (PLNPs) were prepared by a direct emulsification solvent evaporation method. The physical incorporation of PEG was optimized using variable ratios. The produced particles were evaluated to discern their particle size and shape, zeta-potential, entrapment efficiency, and physical stability. The drug-release profiles were studied, and the kinetic model was analyzed. The anticancer activity of the ANS PLNPs on estrogen-positive breast cancer cell lines was determined using flow cytometry. Results: The prepared ANS-PLNPs showed particle sizes in the range of 193.6 ± 2.9 to 218.2 ± 1.9 nm, with good particle size uniformity (i.e., poly-dispersity index of around 0.1). Furthermore, they exhibited relatively low zeta-potential values ranging from −0.50 ± 0.52 to 6.01 ± 4.74. The transmission electron microscopy images showed spherical shape of ANS-PLNPs and the compliance with the sizes were revealed by light scattering. The differential scanning calorimetry DSC patterns of the ANS PLNPs revealed a disappearance of the characteristic sharp melting peak of pure ANS, supporting the incorporation of the drug into the polymeric matrices of the nanoparticles. Flow cytometry showed the apoptosis of MCF-7 cell lines in the presence of ANS-PLNPs. Conclusion: PEGylated polymeric nanoparticles presented a stable encapsulated system with which to incorporate an anticancer drug (ANS) with a high percentage of entrapment efficiency (around 80%), good size uniformity, and induction of apoptosis in MCF-7 cells.
“…dopamine neurotransmission may be a critical factor in the behavioral expression of mania (Joyce et al, 1995;Ranaldi et al, 1999;Mikelman et al, 2017;Wang et al, 2013;Berquist et al, 2015;Paul et al, 2016). Besides to inducing manic-like behaviors, the administration of AMPH in rats can mimic some of the neurochemical alterations associated with BD, including changes in the levels of neurotrophic factors in the brains of animals (Frey et al, 2006;Fries et al, 2015;Walz et al, 2008).…”
Highligths Amphetamine induced behavioral sensitization in rats; Sensitization induced depressive-like behavior after a washout period of 7 days; Sensitization induced anxious-like behavior after a washout period of 7 days; Behavioral alterations was accompanied by alterations in neurotrophins levels.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.