Opioid peptides act at a number of different opioid receptors – the key types being mu (µ), kappa (ĸ) and delta (δ) with different effects depending on where they are in the brain, including:¹⁰

·       - mu-1 receptor – analgesia and dependence

·      -  mu-2 – euphoria, dependence, respiratory depression, pupil constriction (miosis), gastrointestinal effects

·      -  mu-3 – vasodilation

·       - delta receptors – analgesia, GI motility

·       - kappa receptors – analgesia, dysphoria, urination

In analgesia, stimulating mu opioid receptors (MOR) in the mid-brain will trigger a chain of events including inhibition of GABA neurons which releases enkephalin reducing pain sensations. In stress, MOR activation will inhibit noradrenaline release toning down the central stress response.¹⁰

A notable neurotransmitter which can regulate dopamine release is gamma-aminobutyric acid (GABA). GABA_A-activated neurons ordinarily inhibit dopamine neurons, regulating the dopamine mesolimbic reward pathway. Inhibiting GABA secretion stimulates MOR activity, releasing dopamine.^7,10

Compounds such as ethanol, benzodiazepines, or anaesthetics cause structural changes in GABA-A receptors, with tolerance developing as the receptors becoming less responsive to stimulation.⁷