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Placzek AN, Zhang TA, Dani JA: Age dependent nicotinic influences over dopamine neuron synaptic plasticity. Biochem Pharmacol. 2009 Oct 1;78(7):686-92. Epub 2009 May 21.
The dopamine (DA) system of the ventral midbrain plays a critical role as mammals learn adaptive behaviors driven by environmental salience and reward. Addictive drugs, including nicotine, exert powerful influences over the mesolimbic DA system by activating and desensitizing nicotinic acetylcholine receptors (nAChRs) in a subtype-dependent manner. Nicotine induces synaptic plasticity at excitatory synapses onto DA neurons, thereby sending elevated DA signals that participate during the reinforcement of addictive behaviors. While humans and animals of any developmental age are potentially vulnerable to these drug-induced effects, evidence from clinical and epidemiological studies indicates that adolescents have an increased risk of addiction. Although this risk arises from a complex set of variables including societal and psychosocial influences, a contributing factor involves age dependent sensitivity to addictive drugs. One aspect of that sensitivity is drug-induced synaptic plasticity at excitatory synapses onto the dopamine neurons in the ventral midbrain. A single, acute exposure to addictive drugs, including nicotine, produces long-term potentiation (LTP) that can be quantified by measuring the shift in the subtypes of ionotropic glutamate receptors mediating evoked synaptic transmission. This change in glutamatergic transmission is expressed as an increased ratio of AMPA receptors to NMDA receptors at glutamatergic synapses. Age-related differences in the excitability and the nicotine sensitivity within the midbrain dopamine system may contribute to the greater risk of nicotine addiction in adolescent animals and humans. |
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