TY - JOUR T1 - Selective Disruption of Nucleus Accumbens Gating Mechanisms in Rats Behaviorally Sensitized to Methamphetamine JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6687 LP - 6695 DO - 10.1523/JNEUROSCI.0643-05.2005 VL - 25 IS - 28 AU - Anne Marie Brady AU - Stanley D. Glick AU - Patricio O'Donnell Y1 - 2005/07/13 UR - http://www.jneurosci.org/content/25/28/6687.abstract N2 - Behavioral sensitization of psychostimulant-induced locomotor activity in rats has been proposed as a model of addiction and is accompanied by neuroadaptations in the nucleus accumbens and related circuits. Here, we used in vivo intracellular recordings to examine electrophysiological properties of accumbens neurons from animals that did or did not exhibit behavioral sensitization after repeated methamphetamine (5.0 mg/kg; 5 d). Although spontaneous activity of accumbens neurons was virtually unchanged, multiple synaptic interactions controlling membrane potential states were disrupted in sensitized animals. For example, stimulation of the ventral tegmental area attenuated accumbens responses to prefrontal cortex activation in nonsensitized and saline-treated animals, but not in sensitized animals. Acute methamphetamine (0.5 mg/kg) abolished accumbens up and down states in nonsensitized and saline-treated animals, suggesting a disruption of normal information processing in this area. However, acute methamphetamine failed to affect this pattern in accumbens neurons from sensitized animals. These results suggest that both acute and repeated methamphetamine administration can disrupt synaptic interactions in the nucleus accumbens; however, the nature of these alterations depends critically on the extent of behavioral sensitization. It is speculated that the response to acute methamphetamine in nonsensitized and saline-treated animals may be functionally adaptive, whereas the neuroadaptations observed in sensitized animals may be maladaptive and detrimental to accumbens information processing. ER -