The mechanism of action of heroin at the mu (m) opiate receptors
Heroin modifies the action of dopamine in the nucleus accumbens and the ventral tegmental 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 powerful agonist at the mu opioid receptors subtype. 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 results in sustained 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 weak agonist at the opioid kappa and delta receptor subtypes and activation of these receptors has a weak activating effect on the dopaminergic reward pathway.
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The neurobiology of drug addiction. National Institute on drug abuse, National Institutes 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.