The data point to an important but differential role of the amygdala and dorsal raphe nucleus in 5-HTT genotype-dependent vulnerability to cocaine addiction.
These findings have led to the development of recombinant butyrylcholinesterase mutants and viral gene therapy to combat cocaine addiction, along with in-depth studies on the significance of butyrylcholinesterase in obesity.
Across numerous experiments, we and others have identified a critical influence of hypocretin receptor 1 in mediating the behavioral and physiological effects of cocaine which positions this receptor as a potential target for the treatment of cocaine addiction.
A gene network approach showed that the EHMT1, EHMT2, MAPK1, MAPK3, MAP2K1, and HDAC5 genes, which are involved in transcription and chromatin regulation cellular signaling pathways, were also associated with cocaine dependence.
We detected a significant single-nucleotide polymorphism heritability of 28% for CD and identified three genes (two loci) underlying this predisposition: the C1qL2 (complement component C1 q like 2), KCTD20 (potassium channel tetramerization domain containing 20), and STK38 (serine/threonine kinase 38) genes.
We detected a significant single-nucleotide polymorphism heritability of 28% for CD and identified three genes (two loci) underlying this predisposition: the C1qL2 (complement component C1 q like 2), KCTD20 (potassium channel tetramerization domain containing 20), and STK38 (serine/threonine kinase 38) genes.
Evidence that CCR5 knockout mice display fewer dopamine neurons, lower striatal dopamine levels, and reduced locomotor activation compared to wild types also suggest a link between CCR5 receptors and cocaine dependence.
We detected a significant single-nucleotide polymorphism heritability of 28% for CD and identified three genes (two loci) underlying this predisposition: the C1qL2 (complement component C1 q like 2), KCTD20 (potassium channel tetramerization domain containing 20), and STK38 (serine/threonine kinase 38) genes.
A gene network approach showed that the EHMT1, EHMT2, MAPK1, MAPK3, MAP2K1, and HDAC5 genes, which are involved in transcription and chromatin regulation cellular signaling pathways, were also associated with cocaine dependence.
In this same group, interaction analysis demonstrated that the presence of DRD2-T allele and concomitant absence of DRD4-7R allele were associated with risk for crack cocaine addiction.
We found that patients with genetically higher DAT levels had better treatment outcomes with disulfiram pharmacotherapy of cocaine dependence than those with lower DAT levels.(Am J Addict 2019;28:311-317).
Increased expression of Arc, CDK5 and TH, and decrease in DAT protein levels persisted longer after withdrawal, pointing to a neuroplastic lasting effect similar to that involved in cocaine addiction.
One potential mechanism in humans is suggested by findings that ELS interacts with polymorphisms of the GABRA2 gene, encoding α2 subunits of GABAA receptors, to increase the risk for both post-traumatic stress disorder and vulnerability to cocaine addiction.
Further modification of this pendant resulted in retention of KOR agonism and the addition of mu opioid receptor (MOR) partial agonism, a bifunctional profile with potential to be used in the treatment of cocaine addiction.
Further modification of this pendant resulted in retention of KOR agonism and the addition of mu opioid receptor (MOR) partial agonism, a bifunctional profile with potential to be used in the treatment of cocaine addiction.
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.
Therefore, we suggest spinophilin fulfills an essential role in cocaine-induced behavioral sensitization, likely via ERK1/2 phosphorylation and induction of c-Fos and ∆FosB in the striatum, a mechanism that may underlie specific processes in cocaine addiction.
Increased expression of Arc, CDK5 and TH, and decrease in DAT protein levels persisted longer after withdrawal, pointing to a neuroplastic lasting effect similar to that involved in cocaine addiction.
Here, we verify that potent and selective pharmacological activation of NOP receptors is sufficient to reduce relevant facets of cocaine addiction in animal models.
Here, we verify that potent and selective pharmacological activation of NOP receptors is sufficient to reduce relevant facets of cocaine addiction in animal models.
Here, we verify that potent and selective pharmacological activation of NOP receptors is sufficient to reduce relevant facets of cocaine addiction in animal models.