Cross-Generational trans Fat Consumption Favors Self-Administration of Amphetamine and Changes Molecular Expressions of BDNF, DAT, and D1/D2 Receptors in the Cortex and Hippocampus of Rats

Abstract

Amphetamine (AMPH) is an addictive psychostimulant drug whose use has been related to neurotoxicity. Experimentally, AMPH increases anxiety-like symptoms, showing addictive properties. In the last decades, the growing consumption of processed foods has provided an excess of saturated and trans fats in detriment of essential fatty acids, which may modify the lipid profile of brain membranes, thus modifying its permeability and dopaminergic neurotransmission. Here, we assessed the influence of brain incorporation of different fatty acids (FA) on AMPH self-administration. Three groups of young male rats were orally supplemented from weaning with a mixture of soybean oil (SO, rich in n-6 FA) and fish oil (FO, rich in n-3 FA), hydrogenated vegetable fat (HVF, rich in trans fatty acids--TFA), or water (control group). These animals were born from dams that were supplemented with the same fat from pregnancy to lactation. Anxiety-like symptoms and locomotor index were assessed in elevated plus maze and open-field (OF), respectively, while brain molecular expressions of dopaminergic receptors, dopamine transporter (DAT), and BDNF were determined in the cortex and hippocampus. HVF increased the frequency of AMPH self-administration and was associated with reinforcement and withdrawal signs as observed by increased anxiety-like symptoms. Contrarily, SO/FO decreased these parameters. Increased BDNF protein together with decreased DAT expression was observed in the hippocampus of HVF group. Based on these findings, our study points to a harmful influence of trans fats on drug addiction and craving symptoms, whose mechanism may be related to changes in the dopaminergic neurotransmission.

Specific behavioral and cellular adaptations induced by chronic morphine are reduced by dietary omega-3 polyunsaturated fatty acids

“…Drugs of abuse also reduce metabolic status, brain lipid microviscosity, alter dendritic spine morphology, and increase neuroinflammation [63–71], changes which supplemental DHA may reverse [72–76]. Supplementary DHA also decreases stress, anxiety and aggression, behaviors often associated with relapse [77–79]. …”

Effect of exercise rehabilitation on drug withdrawal and its main mechanisms

“…The exercise group was divided into short-term (2 weeks), medium-term (4 weeks) and long-term (6 weeks) swimming training according to the length of exercise time, and then collected the brain tissue disease of animals for molecular analysis. The study found that after morphine injection, the levels of dopamine receptor 1D1R and dopamine receptor 2D2R in the hippocampus of rats increased, and these two kinds of receptors mediate the reward effect of genetic drugs [14]. However, the expression of dopamine transporter, D1R and D2R in each exercise group decreased regardless of the duration of exercise [15].…”

BDNF During Withdrawal

“…Very interestingly, a recent study has shown BDNF alterations in the brain in young adult male rats, 2 days after amphetamine self-administration, depending on the influence of fatty acid consumption. Thus, hydrogenated vegetable fat-supplemented animals are more prone to self-administer amphetamine compared to control group, and BDNF levels in cortex and hippocampus are increased after 2 days of withdrawal (Kuhn et al, 2015).…”