Findings from these studies have led us to recognize the profound disruption of both dynorphin gene expression and kappa opioid receptor gene expression in a setting of chronic cocaine administration and, in turn, have led us to question a possible role of disruption of this system in the acquisition and persistence of cocaine addiction.
Using the human mu opioid receptor gene (OPRM1) as a model system, we have combined these approaches to test a potential role of OPRM1 in substance (heroin/cocaine) dependence.
Our results suggest that changes in Cdk5 levels mediated by DeltaFosB, and resulting alterations in signalling involving D1 dopamine receptors, contribute to adaptive changes in the brain related to cocaine addiction.
Since the serotonin transporter (5HTT) may be involved in modulating effects of cocaine, we investigated whether allelic variants of the 5HTT gene may confer susceptibility to cocaine dependence among African-American individuals.
Although platelet 5-HTT densities are reduced in patients with cocaine dependence compared with healthy volunteers, these genotypic variations in the serotonin transporter do not seem to influence levels of platelet 5-HTT in cocaine-dependent patients or healthy volunteers.
These results support the idea that Cdk5 activity is involved in altered gene expression after chronic exposure to cocaine and hence impacts the long-lasting changes in neuronal function underlying cocaine addiction.
Studies of polymorphisms in the mu opioid receptor gene, which encodes the receptor target of some endogenous opioids, heroin, morphine, and synthetic opioids, have contributed substantially to knowledge of genetic influences on opiate and cocaine addiction.
Modulation of cocaine reward is a novel action of the melanocortin-MC4-R system and could be targeted for the development of new medications for cocaine addiction.
Our data do not support a role for the dopamine D2 receptor gene TaqI A and dopamine D3 receptor gene BalI gene polymorphisms in the susceptibility to cocaine dependence in a Brazilian sample.
This work suggests that variations in the TPH2 gene are not a risk factor for the development of cocaine dependence, but these findings require confirmation in larger, independent samples of cocaine-dependent and control subjects.
We investigated the relationship of a polymorphism in the 5' promoter region of the serotonin transporter gene (5-HTTLPR) with prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP) in a sample of 68 African-American individuals, 35 CD subjects and 33 controls.
Thus, 5-HT(1B) mRNA is upregulated by repeated exposure to cocaine and perhaps by social stress as well; both of these factors are relevant to the risk for relapse in cocaine addiction.
Moreover, seven SNPs covering OPRK1 were examined in the majority of the above subjects (390 cases, including 327 AD, 177 CD and 97 OD subjects, and 358 controls).
Eleven single-nucleotide polymorphisms (SNPs) spanning OPRD1 were examined in 1063 European Americans (EAs) (620 cases with substance dependence (SD), including 557 with alcohol dependence (AD), 225 with cocaine dependence (CD) and 111 with opioid dependence (OD), and 443 controls).
Bakuchiol analogs, especially Delta3,2-hydroxybakuchiol, are monoamine transporter inhibitors involved in regulating dopaminergic and noradrenergic neurotransmission and may have represented potential pharmacotherapies for disorders such as Parkinson's disease, depression, and cocaine addiction.
In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele, p = .0045, assuming an additive genetic model), but in the reverse direction compared with that previously observed for nicotine dependence.