DRUG ADDICTION Molecular mechanisms of opiate and cocaine addiction
Opiates • Subclass of opioids • Two major groups of opiates • A) Natural Alkaloids • B) Semi- Synthetic derivates
Terms important to understand drug addiction • Tolerance • Dependence • Withdrawal
Acute opiate action in the LC • Short term effects of opiates • Decreased firing rates of neurons • Decreased depolarizability of ion channels
Chronic action • Increased depolarizability • Increase firing rates
Consequences of chronic exposure • Tolerance effect • Compensatory mechanism • Upon cessation even more increased firing rates to prevent a drastic drop in firing rates.
Influence on gene expression • Down regulation – alteration in gene expression and regulation of transcription factors • Up regulation – Maintenance of increased rate of gene expression to sustain the chronic opiate state
Drug Reward Initial dose leading to further use due to its desirable effect Rewarding is also involved in other acts of survival Observed primarily in the mesolimbic dopamine System
Chronic cocaine use • Causes phosphorylation and therefore activation of a phosphoprotein called TH in the VTA and vice versa in NAc
Glutamate • Major attention in current research • Cognitive functions and responsible for memory of drug-seeking • Has the NMDA receptors • Increased levels of dopamine – increased levels of glutamate • Glu also responsible for relapse
Current treatments • Glutamate- receptor blockage possibility • GVG ( gamma-vinyl GABA)- blocks the inhibition action of cocaine • Venlafaxine • Cocaine antibodies!