Neural Substrates of Amphetamine-Induced Behavioral Sensitization: Unconditioned (Zero Context) and Conditioned (Switch versus Same Context) Components in c-<b><i>fos</i></b> Overexpression

Abstract

The neural substrates of the unconditioned and conditioned components of amphetamine (AMPH)-induced behavioral sensitization remain unknown. The present study examines the brain activation of rats in response to an AMPH challenge with augmented locomotion in groups receiving chronic AMPH under chloral hydrate anesthetization (i.e., the ‘zero context’) or when tested in the ‘same context’ as a chronic treatment, or when tested in a ‘different context’. The neural activations of the three groups reveal fairly consistent patterns: (a) The substantia nigra is activated in the same context condition and the pure AMPH effect (i.e., the zero context with the unconditioned component), but not in the switch context condition. (b) The ventral pallidum showed Fos expression in the switch context and the same context, but not in the zero context condition. (c) The other nuclei, including the medial prefrontal cortex, nucleus accumbens, caudate putamen, medial thalamus, hippocampus, amygdala, and ventral tegmental area, are activated in all contextual conditions and the pure AMPH effect (the zero context). The context exerts definable effects on the mesocorticolimbic dopamine system on AMPH-induced behavioral sensitization. (d) The ventral pallidum and the substantia nigra activations dissociate the unconditioned component from the conditioned component in behavioral sensitization. Further studies are needed to determine how these two nuclei mediate the effect in terms of primary and conditioned rewards.

Repeated injections of D-Amphetamine evoke rapid and dynamic changes in phase synchrony between the prefrontal cortex and hippocampus

“…Given the emerging evidence of the PFC-HC circuit in processing and integrating information about AMPH and other drug experiences (Lodge and Grace, 2008; Wang et al, 2013), our results suggest that the observed rapid transitions in neural synchrony may affect neural communication and influence drug motivated behavior.…”

Effect of rhynchophylline on the expression of p-CREB and sc-Fos in triatum and hippocampal CA1 area of methamphetamine-induced conditioned place preference rats

“…c-Fos is a highly stable isoform of the FosB immediate early gene family of proteins and accumulates in the nucleus accumbens with repeated treatments with methamphetamine, and levels remain elevated weeks after treatment termination [23]. c-Fosmediated changes in brain gene expression may underpin the capacity of repeated psychostimulant exposure to cause the profound and persistent enhancements of behavior characteristic of sensitization [24]. We selected c-Fos as an indicator, because overexpression of c-Fos protein in the central nervous system (neostriatum) is highly related with the exaggerated compensation of amphetamine-induced rotation observed in animals grafted during adulthood or development [25]: it also provides a direct anatomical index of the postsynaptic response to the presynaptic activation of dopamine neurons with amphetamine [26].…”