Tamoxifen and amphetamine abuse: Are there therapeutic possibilities?

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 amphetamine-induced increase in extracellular dopamine which gives rise to the ‘manic’ effects is due to interaction of amphetamine with the dopamine transporter. We and others have demonstrated that PKC reduces amphetamine-induced reverse transport through the dopamine transporter. In this review, we will outline the actions of tamoxifen as a SERM and further detail another known action of tamoxifen—inhibition of PKC. We will summarize the literature showing how tamoxifen affects amphetamine action. Finally, we will present our hypothesis that tamoxifen, or an analog, could be used therapeutically to reduce amphetamine abuse in addition to treating mania.

Oestradiol influences on dopamine release from the nucleus accumbens shell: sex differences and the role of selective oestradiol receptor subtypes

“…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.…”

Optimized Polyethylene Glycolylated Polymer–Lipid Hybrid Nanoparticles as a Potential Breast Cancer Treatment

“…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 ].…”

The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization: Implications to the animal model of bipolar disorder

“…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).…”