Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

190 III. SUBSTANCES OF ABUSEand the many other neurotransmitter systems impact cocaine reward by actingon dopamine.Corticotropin-releasing factor (CRF) modulates the HPA axis response tostressors. The HPA axis may be implicated in cocaine self-administration, particularlyregarding relapse in cocaine use. Inhibition of circulating corticosteronedecreases intravenous cocaine self-administration in rats. In addition,data suggest that corticosterone secretion does not play a major role in cocaineinducedreinstatement. However, a minimal level is necessary to achieve bothstress-induced and cue-induced cocaine reinstatement, demonstrating an involvementof the HPA axis in the relapse of cocaine use (Goeders, 2002).Intoxication/OverdoseCLINICAL FEATURESWith intoxication, cocaine blocks monoamine neuronal reuptake, initiallyleading to increased dopamine serotonin and norepinephrine availability atreceptor sites. This stimulation of the endogenous pleasure center results ineuphoria, increased energy and libido, decreased appetite, hyperalertness, andincreased self-confidence when small initial doses of cocaine are taken. Exaggeratedresponses such as grandiosity, impulsivity, hyperawareness of the environment,and hypersexuality may also occur. The acute noradrenergic effects ofsmall doses of cocaine include a mild elevation of pulse and blood pressure.Insomnia results from both increased dopamine and norepinephrine concentrations,and decreased serotonin synthesis and turnover.Higher doses of cocaine are accompanied by increasing toxicity. Not onlyis there intensification of the “high,” but anxiety, agitation, irritability, confusion,paranoia, and hallucinations may also occur. Sympathomimetic effectsinclude dizziness, tremor, hyperreflexia, hyperpyrexia, mydriasis, diaphoresis,tachypnea, tachycardia, and hypertension. These symptoms can be accompaniedby a sense of impending doom and may have important ramifications inoverdose situations. Overdose complications may become manifest as muscletwitching, rhabdomyolysis, convulsions, cerebral infarction and hemorrhage,cardiac ischemia and arrhythmias, and respiratory failure.More than any other stimulant, acute intoxication with cocaine is characterizedby convulsions and cardiac arrhythmias. Death may be caused by peripheralautonomic toxicity and/or paralysis of the medullary cardiorespiratory centers(Gay, 1982).Chronic UseIn contrast to acute intoxication, chronic cocaine administration results inneurotransmitter depletion. This is evidenced by a compensatory increase in