The mechanism of action of heroin at the delta (δ) and kappa (κ) opiate receptors
Heroin modifies the action of dopamine in the nucleus accumbens and the ventral tegemental area of the brain – these areas form part of the brain’s ‘reward pathway’. Once crossing the blood-brain barrier, heroin is converted to morphine, which acts as a weak agonist at the delta and kappa opioid receptors subtypes. This binding inhibits the release of GABA from the nerve terminal, reducing the inhibitory effect of GABA on dopaminergic neurones. The increased activation of dopaminergic neurones and the release of dopamine into the synaptic cleft results in activation of the post-synaptic membrane. Continued activation of the dopaminergic reward pathway leads to the feelings of euphoria and the ‘high’ associated with heroin use. Morphine is a powerful agonist at the opioid mu receptor subtype and activation of these receptors has a strong activating effect on the dopaminergic reward pathway.
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References
The neurobiology of drug addiction. National Institute on drug abuse, National Institute of Health. http://www.nida.nih.gov/Teaching2/teaching5.html. Accessed on 30 January 2003.
Opioid analgesics and antagonists. In: Basic and clinical pharmacology, 8th edition. Katzung BG. USA: The McGraw Hill Companies, Inc, 2001:512–531.