Mechanism of action for opiates

 

Opiates cause euphoria by 2 mechanisms. They first reduce the excitability of neurones by acting on various opioid receptors, such as μ, δ, κ and σ, found in both the brain and the spinal cord. These receptors are linked to G proteins and result in the opening of potassium channels, therefore causing hyperpolarisation and reduced neuronal excitability.

 

GABA is an inhibitory neurotransmitter than reduces the amount of dopamine released. Opiates can reduce the amount of GABA released therefore reducing its inhibitory effects and resulting in more dopamine being present. Dopamine is the pleasure inducing neurotransmitter in the brain.

 

Physical dependence can occur as a result of the long term adaptive changes from the inhibition of adenylyl cyclase and activation on MAP kinase. cAMP production is initially inhibited by the opiates, so the body adapts to produce more via other mechanisms. Once the opiate is withdrawn cAMP is produced in an abundance and results in neuronal hyperactivity and cravings.