Dynorphin

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DYNORPHIN

Dynorphin is a neuropeptide transmitter; it is an Opioid peptide, a member of the endorphin family of peptides. All neurotransmitters like Dynorphin have receptors. Its greatest affinity is for the Kappa opioid receptor. Dynorphin's role in drug abuse was originally anticipated based on its location in anatomical areas strongly associated with the mechanism of action of drugs of abuse. It is localized in the Nucleus Accumbens, Amygdala, and Ventral Tegmental Area.

Dynorphin induces feelings of dysphoria, or despair. This was first documented in animals, and later confirmed in humans. It is surprising because the best known opiate-like drugs are morphine and heroin, and they present great abuse liability since they illicit feelings of euphoria and absence of pain. However, there seem to be two opioid systems controlling behavior one influencing feelings of Reward (through-endorphins) and one influencing feelings of Aversion, (through dynorphin). The physiological substrate underlying the effects of dynorphins is believed to be at the level of the Mesolimbic Dopamine neurons in the ventral tegmental area. Dynorphin tonically inhibits the firing of dopamine neurons, thus preventing its release in the striatum. Elevations of dopamine levels in the nucleus accumbens are believed to underlie the reinforcing properties of many Psychostimulant-like drugs, as well as Opiates.

Due to the Adverse feeling associated with Withdrawal from many drugs of abuse, the dynorphin system has been implicated in contributing to this state. Studies have found that there are long-term changes in dynorphin levels in brain areas associated with drug abuse, and that these changes also exist during withdrawal. Prenatal exposure to cocaine also effects the levels of dynorphin in the brain. These changes are present in both animal and human models of drug abuse. Since drugs modulate dynorphin systems, we can gain an understanding of how drugs work in the brain by studying the dynorphin system.