Jamil, Nur Khadijah Muhamad
(2020)
Assessment of dopamine receptor drd4 and drd5 mrna expression in peripheral blood lymphocytes of opioid & amphetamine type stimulant dependent Malay men undergoing methadone maintenance therapy.
Masters thesis, Universiti Sains Malaysia.
Abstract
In Malaysia and throughout the Asian region the mixed opioid and
amphetamine type stimulants dependence is highly prevalent which has become a
major health problem. Opioids and amphetamine-type stimulants (ATS) exert their
effect by altering natural dopamine neurotransmission in the brain to achieve the
ultimate goal of an extracellular hyper-dopamine state hence resulting drug reward
effect. Dopamine actions are mediated by specific G proteins coupled receptors of
two distinct families; D1-like receptor subtypes (D1 and D5) and the D2-like receptor
subtypes (D2, D3, and D4). Evidence from previous studies has suggested that
peripheral dopamine systems reflect the central dopamine system’s activity and
pathology, especially in neuropsychiatric diseases. Studies have been carried out
widely on central dopamine systems, while investigation of dopamine systems in
various peripheral organs is still limited. It has been reported that peripheral blood
lymphocytes express dopamine in peripheral systems. In this study, we investigated
the difference in the mRNA expression of the dopamine receptors DRD4 and DRD5
in peripheral blood lymphocytes of ATS and opioid dependent Malay male subjects
undergoing methadone maintenance treatment and healthy Malay male serving as
control subjects. A total of 72 participants with 36 drugs dependent subjects and 36
control subjects were recruited from various parts of Kuala Terengganu, Terengganu
according to inclusion and exclusion criteria. Demographic data including age, height
weight, body mass index and blood pressure of all participants were recorded. A
questionnaire form was given to the drug dependent subjects to assess their drug
addiction status. Informed and written consent was obtained, and blood samples were
collected. RNA was extracted from lymphocytes. The mRNA expression of the
dopamine receptors DRD4 and DRD5 in peripheral blood lymphocytes was assessed
by real-time PCR method. The demographic data of the subjects were calculated using
Mann Whitney Test. The p-value 0.05 was used for the statistical significance. There
was a significant difference between drug dependent subjects and control subjects for
age and systolic blood pressure parameters while other parameters were not
statistically significant. The DRD4 mRNA expression level is significantly reduced in
lymphocytes of drug dependent subjects compared to control subjects (p=0.039).
However, DRD5 mRNA expression level in lymphocytes of drug dependent subjects
was not statistically significant (p=0.251). In conclusion, drug dependent subjects on
mixed opioid and ATS dependence undergoing methadone maintenance treatment
may exhibit different patterns of dopamine receptors DRD4 and DRD5 mRNA
expressions in the peripheral lymphocytes. Further studies are recommended to
support the findings of the present study.
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