Addictive properties

Cocaine and desipramine inhibit the reuptake of monoamine neurotransmitters whereas amphetamine, which is a phenylalkylamine - similar in structure to the catecholamines, see Fig. 4 - competes for uptake and more importantly, evokes efflux of the monoamine neurotransmitters. All of them exert antidepressant effects. Cocaine and amphetamine are addictive whereas tricyclic antidepressants and their modern successors are not. The corollaty of the addictive properties is interference with DAT activity. Blockade of DAT by cocaine or efflux elicited by amphetamine produces a psychostimulant effect despite the different mechanisms even the experienced individual can hardly discern their actions. Because of the risk associated with inhibiting DAT mediated dopamine clearance the antidepressant effects of psychostimulants has not been exploited. 

Pich, E., Pagliusi, S., Tessari, M., Talabot-Ayer, D., Huijsduijnen, R.H.v., Chiamulera, C. Common neural substrates for the addictive properties of nicotine and cocaine. Science. 275 83, 1997. 

Nicotine is responsible for the highly addictive properties of tobacco... 

Nicotine is responsible for the highly addictive properties of tobacco products. Addiction occurs in 30% of those who experiment with tobacco products, and more than 80% of those who attempt to quit smoking will relapse within a year. Withdrawal from nicotine produces a syndrome characterized by nicotine craving as well as dysphoria, anxiety, irritability, restlessness and increased appetite. It is treated with nicotine replacement therapies, such as nicotine gum and patches, and/or with buproprion, a drug that is classified as an antidepressant but has multiple and complex effects in brain. Buproprion reduces craving in some smokers. Nicotine addiction has been reviewed recently at cellular and systems levels [38-41]. 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

Indirect mechanisms Nicotine has indirect effects on monoamine systems. A considerable amount of research has examined the relationships between nicotine and dopamine activity in the brain, in light of dopamine s role in reinforcement and nicotine s addictive properties. Nicotine increases dopamine turnover in the striatum and cerebral cortex (Clarke and Reuben 1996 Tani et al. 1997 Nanri et al. 1998). It also increases burst activity in dopamine neurons of the ventral tegmental area (VTA), a primary source of dopamine to the forebrain (Nisell et al. 1995 Fisher et al. 1998). Such a firing pattern in the VTA is associated with processes of reinforcement, learning, and cognitive activity. Nicotine actions on dopaminergic neurons occur at both somatodendritic sites and synaptic terminals. Further, both systemic nicotine and direct administration into the VTA increase dopamine release in the nucleus ac-... 

A dependency syndrome occurs in many who chew areca (Trivedy et al. 1999). This is not entirely suprising because other cholinergic stimulants (e.g., tobacco) also have addictive properties, and arecoline causes a release of dopamine like many other abused drugs. Use of areca persists despite adverse health effects—one of the criteria for addiction. 

Chewing leaves of the khat shrub is practiced in parts of East Africa and the Arabian peninsula (Kalix 1988 Widler et al. 1994). Some estimate daily use at 5 million portions. Use in the West is less common, but has increased somewhat. More common in the United States has been use of the synthetic drug methcathinone (or "cat"), which is derived from khat alkaloids. Only the fresh khat leaves are pharmacologically active, so for some time use was limited to local areas that grew the plant. However, with air transportation, use has spread with emigrants in Europe and the United States. Because of its pharmacological similarities to amphetamine and its addictive properties, khat has been listed on Schedule I of the United Nations Convention on Psychotropic Substances. 

Although tobacco Nicotiana tabacum) is widely known for its stimulant and addictive properties, its principal psychoactive constituent, nicotine, has become a candidate drug for improving cognition (Le Houezec 1998 Lawrence and Sahakian 1998 Newhouse et al. 1997). Clearly, the health risks associated with smoking tobacco preclude its clinical use, but nicotine delivered in other forms may be useful. 

Pich EM, Paghusi SR, Tessari M, Talabot-Ayer D, Hooft v H, Chiamulera C (1997) Common neural substrates for the addictive properties of nicotine and cocaine. Science 275 83-86 PidopUchko VI, DeBiasi M, Williams JT, Dani JA (1997) Nicotine Activates and Desensitizes Midbrain Dopamine Neurons. Nature 390 401 04 PietUa K, Ahtee L (2000) Chronic nicotine administration in the drinking water affects the striatal dopamine in mice. Pharmacol Biochem Behav 66 95-103 Puttfarcken PS, Jacobs I, Faltynek CR (2000) Characterization of nicotinic acetylcholine receptor-mediated [ H]-dopamine release from rat cortex and striatum. Neuropharmacology 39 2673-2680... 

The Neuronal Pathways Mediating the Behavioral and Addictive Properties of Nicotine... 

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