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Background: Human neuroimaging studies indicate that the amygdala plays a key role in cocaine addiction. One key plasticity factor that modulates effects of cocaine on the brain is Brain-Derived Neurotrophic Factor (BDNF). A wealth of evidence shows that cocaine exposure alters BDNF signaling in corticolimbic structures, but, surprisingly, such evidence is very limited for the amygdala. Additionally, while BDNF is strongly regulated by serotonin levels and inherited serotonin transporter down-regulation is associated with increased vulnerability to cocaine addiction, the effects of serotonin transporter genotype on BDNF signaling in the amygdala under naïve and cocaine exposure conditions are unknown., Methods: We measured BDNF signaling in the central amygdala of wild-type and serotonin transporter knockout rats 24 h into withdrawal from long-access cocaine self-administration., Results: In wild-type rats mature BDNF (mBDNF) protein levels were decreased, whereas the phosphorylation of its receptor TrkB as well as of its intracellular signaling molecules Akt and ERK1 were increased. mBDNF protein expression and its signaling in cocaine-naïve serotonin transporter knockout rats resembled that of wild-type rats with a history of long-access cocaine self-administration. Interestingly, cocaine-exposed serotonin transporter knockout rats showed increased BDNF levels, with no signs of phospho-TrkB receptor coupling to phospho-Akt and phospho-ERK1., Conclusions: Long-access cocaine self-administration dysregulates BDNF signaling in the central amygdala. Vulnerability to cocaine addiction is associated with dysregulation of this signaling., (Copyright © 2019 Elsevier B.V. All rights reserved.)

It has recently been proposed that the increased reinforcing properties of cocaine and ecstasy observed in rats with a genetic deletion of serotonin transporters are the result of a reduction in the psychostimulant-induced release of serotonin. Here we provide the neurochemical evidence in favor of this hypothesis and show that changes in synaptic levels of dopamine or noradrenaline are not very likely to play an important role in the previously reported enhanced psychostimulant intake of these serotonin transporter knockout rats. The results may very well explain why human subjects displaying a reduced expression of serotonin transporters have an increased risk to develop addiction., (Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.)

Individuals are known to differ in their sensitivity to cocaine. Cocaine is known to inhibit the re-uptake of monoamines. The response to cocaine has also been found to depend on monoamines inside reserpine-sensitive storage vesicles. The present study examined the effects of reserpine (1-2 mg/kg) on cocaine-induced behavior (10-15 mg/kg) in Low Responders (LR) and High Responders (HR) to novelty rats. LR displayed less cocaine-induced walking, wall rearing, free rearing and stereotyped behavior than HR did. The dose of 1 mg/kg of reserpine decreased cocaine-induced walking, wall rearing, free rearing and stereotyped behavior in LR, but not in HR. A dose of 2 mg/kg of reserpine was required to inhibit cocaine-induced behavior in HR. Combining these behavioral findings with our previously reported neurochemical finding that a higher dose of reserpine was required to inhibit the accumbal dopamine response to cocaine in HR than in LR (Verheij et al., 2008), suggests that HR are more sensitive to the behavioral effects of cocaine than LR because cocaine can release more monoamines from storage vesicles in HR than in LR. Our behavioral data also demonstrate that the individual differences in sensitivity to reserpine are not only limited to the dopaminergic system of the nucleus accumbens., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Individual differences in responses to mild, acute stressors in laboratory animals have commonly been observed in behavioural tests and at the level of hypothalamic-pituitary-adrenal axis responses. These differences are associated with dopamine transmission in the nucleus accumbens. Although the effect of mild stressors on dopamine transmission has been studied with microdialysis, it has not been studied at the level of the catecholaminergic network in the nucleus accumbens. In this study we have used microdialysis to measure extracellular concentrations of dopamine in vivo and immunocytochemistry for the enzyme tyrosine hydroxylase to assess the effect of a single exposure to novelty on the neurochemistry of the nucleus acc umbens in apomorphine-susceptible and apomorphine-unsusceptible rats. These rats are a valid animal model for studying individual differences in responses to environmental stressors and drugs of abuse. We demonstrated that a mild stressor like novelty increased the extracellular concentration of dopamine in the nucleus accumbens in apomorphine-susceptible rats to a larger and longer-lasting degree than in apomorphine-unsusceptible rats. Furthermore we demonstrated that novelty increased the tyrosine hydroxylase-immunoreactive fibre network in the nucleus accumbens shell of apomorphine-susceptible rats, which are rats that are particularly reactive to stressors, but not in the shell of apomorphine-unsusceptible rats, which are rats that are relatively stress-resistant. In conclusion, we have shown that the accumbal dopaminergic system of apomorphine-susceptible rats is more sensitive to an environmental stressor than that of apomorphine-unsusceptible rats. Combined with the fact that these animals also differ in their sensitivity to drugs of abuse, which are known to affect the dopaminergic system, these data provide a solid basis for further studying the differences in the dopaminergic responsiveness to drugs of abuse between apomorphine-susceptible and apomorphine-unsusceptible rats.