High-frequency deep brain stimulation (dbs) is a novel therapeutic address against drug addiction. the mechanism by which this is succeeded still unknown. dopaminergic signaling is specific neurotransmitter of drug-reward circuity and lateral hypothalamus (lh) is involved in dopamine signaling and reward pathway. we aimed effect of lh high frequency stimulation in dopamine and c-fos expression in the prefrontal cortex.
Methods
Electrodes were implanted into the lh bilaterally and after recovery lh were stimulated with dbs (130 hz pulse repetition frequency, 150 µa pulse amplitude, and 100 μs pulse width) and treated with morphine (5mg.kg) for four consecutive days. then, rats were sacrificed and prefrontal cortex were separated for western blot analysis and rt-pcr.
Results
Dbs and morphine treatment decreased the cellular level of both d1-like family compared with morphine treated rats without dbs in the prefrontal cortex. dbs with concomitant morphine increased d2-like family in comparison to morphine received rats in the prefrontal cortex. also, dbs and morphine treatment increased c-fos expression compared with morphine received group.
Conclusion
Stimulation of lh as a site against drug reward might influence dopaminergic system and inhibits reward system in the brain of morphine addicted subjects. also, stimulation of lh increased c-fos in morphine received rats; an immediate early gene involved in neuronal plasticity. based on these data, targeting dbs of lh might be a novel candidate against addiction.
Keywords
High frequency stimulation; morphine; dopamine receptors; c-fos; lateral hypothalamus; rat
