Assessment and Management of Opioid Use Disorder, Withdrawal, and Intoxication Syndromes Neurobiology of Opioid Dependence and withdrawal Opioids act at specific opioid receptors in the central nervous system. Stimulation of these receptors suppresses the firing rate of noradrenergic neurons in the midbrain, thus causing CNS depression and reduction of anxiety. Euphoria is also because of the release of dopamine at nucleus coeruleus in the forebrain by dopaminergic neurons that originate in the ventral tegmental area in the midbrain. Opioid use causes reinforcement of the drug-taking behaviours because of these euphoric effects and the relief from anxiety. Repeated usage also causes neuroadaptive changes in these neurons, such that progressively less dopamine release in the nucleus coeruleus and less suppression of midbrain noradrenergic cells lead to reduced effects or increased doses being taken by the person (tolerance). When the person stops taking the drug, overexcited noradrenerg