Title: Reward Pathway in Brain and Alcohol Dependence: A Co-Relation Study in Wistar Rats to Show the Effect on Brain Dopamine, Dihydrophenylacetic Acid (DOPAC) and Homovanilic Acid (HVA)

Authors: Janki Malli, Nimmy Chacko, Vijayanarayana K

 DOI:  https://dx.doi.org/10.18535/jmscr/v5i4.72

Abstract

Humans, as well as other organisms engage in behaviors that are rewarding. The pleasurable feelings provide positive reinforcement so that the behavior is repeated. Each of the naturally rewarded behaviors is required for the survival of the species, so the reward pathway is a crucial part of the brain, as well as a key in understanding addictions. The major part of reward pathway is the ventral tegmental area (VTA). The neurons of the VTA contain the neurotransmitter dopamine which is released in the nucleus accumbens. This pathway is activated by a rewarding stimulus. Dopamine is released particularly in areas such as the nucleus accumbens and prefrontal cortex by naturally rewarding experiences such as food, drugs, and neutral stimuli that become associated with them. Dopamine is also a neurohormone released by the hypothalamus. Dopamine is commonly associated with the pleasure system of the brain, providing feelings of enjoyment and reinforcement to motivate a person to perform certain activities. Chemical or surgical interruption of this dopaminergic pathway impairs drug seeking behavior in many experimental situations. Deletion of D2 dopamine receptors in transgenic mouse strain eliminated the reward properties of morphine administration. Dopaminergic antagonist, like Quetiapine and Olanzapine were studied as new pharmacotherapy for treating alcohol dependence by analysing dopamine level in rat brain homogenate using HPLC. Analysis of dopamine level in rat brain homogenate using HPLC showed that the peak area of olanzapine and quetiapine group was 94.94mV.s and 147.9mV.s respectively which is less than peak area of alcohol 190.69mV.s. This indicates that alcohol abusestimulates the reward pathway which increases the level of dopamine in ventral tegmental area of the brain which is antagonised by dopamine antagonists.Since dopamine plays an important role in alcohol dependence (positive reinforcement), D2 dopaminergic antagonists like Quetiapine and Olanzapine provides a new role in pharmacotherapy of alcohol dependence and alcohol withdrawal.

Keywords: Alcohol dependence, dopamine, reward pathway, mesolimbic dopaminergic pathway, dopamine antagonists, Quetiapine, Olanzapine. 

References

 

Corresponding Author

Janki Malli

Department of Pharmacology, NGSM Institute of Pharmaceutical Sciences

Paneer, Deralakatte, Mangalore, Karnataka, India