IntroductionThe principal routes of cocaine administration are oral, intranasal, intravenous, and inhalation.The slang terms for these routes are, respectively, "chewing," "snorting," "mainlining," "injecting," and "smoking" (including freebase and crack cocaine).Cocaine use ranges from occasional use to repeated or compulsive use, with a variety of patterns between these extremes.There is no safe way to use cocaine.Any route of administration can lead to absorption of toxic amounts of cocaine, allowing to acute cardiovascular or cerebrovascular emergencies that could result in sudden death.Repeated cocaine use by any route of administration can produce addiction and other adverse health consequences.Those who snort or sniff cocaine through their noses suffer damage to their nasal and sinus passages.These include nasal crusting, nosebleeds, nasal congestion, irritation, facial pain caused by sinusitis and hoarseness.Cocaine addiction changes the responsiveness of the brain to various neurotransmitters or chemicals.The development of drug addiction involves persistent cellular and molecular changes in the Central Nervious System.The brain dopamine, GABA and glutamate systems play key roles in mediating drug-induced neuroadaptation.We show some physiological changes that can occur in some key pathways in which glutamate, dopamine and GABA receptors are involved.These chemical changes cause different effects in users, including: anxiety, confusion, dizziness, psychosis, headaches and nausea.Cocaine use and addiction affects the sympathetic nervous system (which controls automatic functions such as breathing, heartbeat, etc.).This system secretes adrenaline which raises ones heart rate, narrows blood vessels and significantly increases blood pressure.Chest pain, heart attacks and strokes are common side effects of cocaine use.The most widely studied neurobiological characteristic of cocaine addiction is the role played by dopamine transmission.It is clear that enhanced dopamine transmission in neurons projecting from the ventral mesencephalon to the limbic forebrain, including the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), is the pharmacological target for cocaine-induced reinforcement and locomotor stimulation (O'Brien., 2001) However, persistence of the behavioral characteristics of cocaine addiction, such as paranoia (sensitization) and the propensity to relapse years after the acute rewarding effects of the drug have disappeared, indicates that there must also be neuronal substrates undergoing Addictions -From Pathophysiology to Treatment 104 long-term neuroplastic changes.Although studies have endeavored to identify enduring changes in dopamine transmission that might underlie behavioral sensitization and the reinstatement of drug-seeking (relapse), the results have not been entirely consistent with an obligatory role for dopamine.Addiction can be viewed as a form of drug-induced neural plasticity.One of the bestestablished molecular mechanisms of addiction is up-regulation of the cAMP second messenger pathway, which occurs in many neuronal cell types in response to chronic administration of opiates or other drugs of abuse.This up-regulation and the resulting activation of the transcription factor CREB appear to mediate aspects of tolerance and dependence.In contrast, induction of another transcription factor, termed 1FosB, exerts the opposite effect and may contribute to sensitized responses to drug exposure.Knowledge of these mechanisms could lead to more effective treatments for addictive disorders.Cocaine Dopamine Tansporter (DAT) Norepinephrine Transporter (NET) Serotonine Transporter (SERT)