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BDNF and Drug Dependence
Brain-derived neurotrophic factor (BDNF) is a growth factor involved in neuronal plasticity that is expressed after chronic administration of drugs of abuse and may play a crucial role in chronic opiate effects. Vargas-Perez et al. (p. 1732, published online 28 May) found that BDNF was directly involved in the switching mechanism in the ventral tegmental area, from an opiate-naïve, dopamine-independent drug reward substrate to an opiate-dependent, dopamine-dependent motivational substrate. In the ventral tegmental area, BDNF changed the action of GABA-A receptors from inhibitory to excitatory. This change led to behavioral changes that defined a neurobiological boundary between the acute phase of drug-taking and addiction.
The neural mechanisms underlying the transition from a drug-nondependent to a drug-dependent state remain elusive. Chronic exposure to drugs has been shown to increase brain-derived neurotrophic factor (BDNF) levels in ventral tegmental area (VTA) neurons. BDNF infusions into the VTA potentiate several behavioral effects of drugs, including psychomotor sensitization and cue-induced drug seeking. We found that a single infusion of BDNF into the VTA promotes a shift from a dopamine-independent to a dopamine-dependent opiate reward system, identical to that seen when an opiate-naïve rat becomes dependent and withdrawn. This shift involves a switch in the γ-aminobutyric acid type A (GABAA) receptors of VTA GABAergic neurons, from inhibitory to excitatory signaling.