dependence Upregulation of the signal transduction pathway in the locus coeruleus by has been implicated as the mechanism responsible for certain aspects of opioid-induced physical dependence. The temporal course of withdrawal correlates with LC firing, and administration of α2 agonists into the locus coeruleus leads to a decrease in LC firing and norepinephrine release during withdrawal. A possible mechanism involves upregulation of NMDA receptors, which is supported by the attenuation of withdraw by NMDA receptor antagonists. Physical dependence on opioids has been observed to produce an elevation of extracellular glutamate, an increase in NMDA receptor subunits NR1 and NR2A, phosphorylated CaMKII, and c-fos. Expression of CaMKII and c-fos is attenuated by NMDA receptor antagonists, which is associated with blunted withdrawal in adult rats, but not neonatal rats While acute administration of opioids decreases AMPA receptor expression and depresses both NMDA and non-NMDA excitatory postsynaptic potentials in the NAC, withdrawal involves a lowered threshold for LTP and an increase in spontaneous firing in the NAc. Diagnosis DSM classification "Substance dependence", as defined in the DSM-IV, can be diagnosed with physiological dependence, evidence of tolerance or withdrawal, or without physiological dependence. DSM-IV substance dependencies include: 303.90 Alcohol dependence 304.00 Opioid dependence 304.10 Sedative, hypnotic, or anxiolytic dependence (including benzodiazepine dependence and barbiturate dependence) 304.20 Cocaine dependence 304.30 Cannabis dependence 304.40 Amphetamine dependence (or amphetamine-like) 304.50 Hallucinogen dependence 304.60 Inhalant dependence 304.80 Polysubstance dependence 304.90 Phencyclidine (or phencyclidine-like) dependence 304.90 Other (or unknown) substance dependence 305.10 Nicotine dependence Management Addiction is a complex but treatable condition. It is characterized by compulsive drug craving, seeking, and use that persists even if the user is aware of severe adverse consequences. For some people, addiction becomes chronic, with periodic relapses even after long periods of abstinence. As a chronic, relapsing disease, addiction may require continued treatments to increase the intervals between relapses and diminish their intensity. While some with substance issues recover and lead fulfilling lives, others require ongoing additional support. The ultimate goal of addiction treatment is to enable an individual to manage their substance misuse; for some this may mean abstinence. Immediate goals are often to reduce substance abuse, improve the patient's ability to function, and minimize the medical and social complications of substance abuse and their addiction; this is called "harm reduction". Treatments for addiction vary widely according to the types of drugs involved, amount of drugs used, duration of the drug addiction,