ABSTRACT
During abstinence (withdrawal phenomema)
The opiates and their synthetic analogs are the most effective analgesics known, but at the same time can produce tolerance, dependence, and addiction. Opiate drugs bind to three subtypes of opioid receptors, denoted l, j, and d, which are members of the G-protein-coupled receptor family. This coupling results in inhibition of adenylate cyclase (AC), activation of inwardly rectifying potassium (K) channels, and inhibition of the sodium current. Opioid receptors thus typically mediate inhibitor responses that reduce membrane excitability and reduce the likelihood of cell firing. Morphinelike opiates, including heroin (diamorphine), a widely abused substance, are both analgesic and addictive, and interact with greatest affinity with the l receptor. These drugs appear to produce both reward and reinforcement by means of activation by disinhibition – i.e. they inhibit inhibitory neurons affecting dopaminergic transmission of the ventral tegmental area, releasing dopamine in the nucleus accumbens – and by direct binding to opioid receptors in the nucleus accumbens, independent of dopamine.
