Repeated cocaine exposure induces sensitization of ultrasonic vocalization in rats.

Ultrasonic vocalization at 55kHz (55kHz-USVs) by rodents has been proposed to be a behavioral manifestation of affectively positive incentive motivation. To examine the extent to which 55kHz-USV emissions correlate with cocaine-induced locomotor activity, we measured cocaine-induced 55kHz-USVs and their relationship to cocaine-induced locomotor sensitization in rats. We demonstrate that similar to locomotor responses, 55kHz-USVs are also sensitized by exposure to cocaine.

Stress-induced, glucocorticoid-dependent strengthening of glutamatergic synaptic transmission in midbrain dopamine neurons.

Stress facilitates development of addictive behaviors in part by stress-induced increase in the strength of glutamatergic synapses at dopamine (DA) neurons within the ventral tegmental area (VTA). Here, we further demonstrate that this stress-induced synaptic adaptation is glucocorticoid-dependent and is progressively developed. Activation of glucocorticoid receptors (GRs) either by in vivo injection of dexamethasone (Dex) or incubation of the VTA slice with Dex potentiate the synaptic strength of glutamatergic synapses at VTA DA neurons, whereas preventing the activation of GRs by Ru486 abolishes this effect.

Homeostatic recovery of downstate-upstate cycling in nucleus accumbens neurons.

Homeostatic plasticity is a powerful cellular mechanism through which neurons adjust intracellular and intercellular resources to stabilize their functional output through the ever-changing environment. Here, we report a novel form of homeostatic plasticity that nucleus accumbens (NAc) neurons use to regain their functionally active state once it is lost. In vivo, NAc neurons periodically alternate between a functionally active upstate and a functionally quiescent downstate.

CREB modulates the functional output of nucleus accumbens neurons: a critical role of N-methyl-D-aspartate glutamate receptor (NMDAR) receptors.

Nucleus accumbens (NAc) medium spiny neurons cycle between two states, a functionally inactive downstate and a functionally active upstate. Here, we show that activation of the transcription factor cAMP-response element-binding protein (CREB), a common molecular response to several drugs of abuse, increases both duration of the upstate and action potential firing during the upstate. This effect of CREB is mediated by enhanced N-methyl-d-aspartate glutamate receptor (NMDAR) function: increased CREB activity increases both NMDAR-mediated synaptic currents and surface level of NMDARs, while inhibition of NMDARs abolishes the effect of CREB on upstate duration.