Brain Stimulation Reward - Modulation With Drugs - Dopamine Antagonists and Agonists

Dopamine Antagonists and Agonists

Drugs that alter the potency of BSR in either an antagonistic or synergistic manner are predominantly dopamine antagonists and agonists. The mechanism of synergism between addictive drugs and brain stimulation is the summation effect within or at the synapses of the mesolimbic system. Although dopamine plays a fundamental role in the rewarding effects of brain stimulation and abusive drugs, the exact nature of it role is still unclear, and since the reward circuitry is multisynaptic, dopamine is not the only reward transmitter. Dopamine neurons play an important role in incentive motivation and reinforcement associated with electrical stimulation to the MFB. Initially, stimulation of the MFB was thought to activate the dopamine fibers directly, it is now believed the stimulation at the MFB selectively activates afferent input into the dopamine system.

Cholinergic agents are rewarding when injected into the ventral tegmental area (VTA). Opiates including Mu and Delta opioids appear to have the strongest rewarding effects through afferents to the mesolimbic dopamine systems, and the presumed mechanism of action involves the disinhibition of the dopamine system by inhibition of nearby GABAergic neurons. Dopamine and opiate antagonists are competitive antagonists of BSR, and they impair the synaptic transmission of the reward signal either across the dopaminergic synapse or across a synapse in which dopamine has a modulatory function. On the other hand, drugs of abuse have been shown to synergize with BSR by reducing the BSR thresholds for amount of stimulation required as well as act to negate the effects of a reward antagonist. BSR synergistic drugs include: amphetamines, cocaine, heroin, morphine, nicotine, phenylcyclidine, mu and delta opioids, and cannabis. These synergistic drugs summate with BSR and serve as rewards themselves by elevating the dopamine concentration at forebrain dopamine nerve terminals, including the nucleus accumbens.

Read more about this topic:  Brain Stimulation Reward, Modulation With Drugs

Famous quotes containing the word antagonists:

    There is a persuasion in the soul of man that he is here for cause, that he was put down in this place by the Creator to do the work for which he inspires him, that thus he is an overmatch for all antagonists that could combine against him.
    Ralph Waldo Emerson (1803–1882)