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Abstract

Forensic Science & Addiction Research

A Schematic Overview of Addiction: Molecular Effects of Cocaine, Methamphetamine and Morphine on Limbic Neurons

Submission: March 29, 2019;Published: April 30, 2019

DOI: 10.31031/FSAR.2018.04.000599

ISSN: 2578-0042
Volume4 Issue4

Abstract

Abuse of methamphetamine, cocaine and morphine is an increasing global problem. According to 2018 UNODOC report between 2012 and 2016, 151 millions of people used cannabis; 146 millions of people consumed cocaine; 275 millions of people used opioids and opiates; 131 millions of people consumed amphetamines. According to another Global Drug Survey-2017, the figures of addiction may be much worse than the expected. People use cocaine and amphetamines because these drugs increase the dopamine release in ventral tegmental area (VTA), nucleus accumbens (NA) and prefrontal cortex, brain regions which take part in the reward-pleasure circuitry. They also play major roles in the development of addiction. In the review the mechanism of action of amphetamines, cocaine and morphine are explained in a very clean schematic way; explaining why people get addicted to these drugs. Cocaine binds strongly to the dopamine-reuptake transporter, preventing the reuptake of dopamine into the nerve terminal. Because of this blocking effect, dopamine remains at high concentrations in the synapse and continues to affect adjacent neurons, producing the characteristic cocaine “high”.

Activated D1 receptor activates the PKA signaling pathway, and this pathway plays a critical role in mediating the behavioral responses to cocaine administration. Cocaine-induced neuroadaptations, including dopamine depletion, may underlie craving and hedonic dysregulation. Acute administration of amphetamine induces phosphorylation of cAMP response element-binding protein (CREB) and expression of several immediate early genes (IEGs), such as c-fos. The IEGs is likely to initiate downstream molecular events, which may have important roles in the induction and maintenance of addictive states. Chronic exposure to amphetamine induces a unique transcription factor delta FosB, which plays an essential role in long-term adaptive changes in the brain. Morphine can cause indirect excitation of VTA dopamine neurons by reducing inhibitory synaptic transmission mediated by GABAergic neurons. The chronic use of morphine is characterized by adaptive changes in neurons and neuronal communication; such adaptations (e.g., ‘super-activation’ of adenylyl cyclase) must underlie altered behavior associated with morphine dependence and withdrawal syndrome, as well as drug-induced craving and relapse to drug use.

Keywords: Addiction; Cocaine abuse; Methamphetamine abuse; Opiate abuse; Morphine; Ventral tegmental are; VTA; Nucleus accumbens; NA; CREB; c-fos; Dopamine; D1 receptor; NMDA-R

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