The nature of neuroadaptations in the genesis of escalated cocaine taking remains a topic of considerable interest. Intermittent social defeat stress induces both locomotor and dopaminergic cross-sensitization to cocaine, as well as escalated cocaine self-administration. The current study examines the role of corticotropin releasing factor receptor subtypes 1 and 2 (CRFR 1 , CRFR 2 ) within the ventral tegmental area (VTA) during social defeat stress. This study investigated whether injecting either a CRFR 1 or CRFR 2 antagonist directly into the VTA before each social defeat would prevent the development of later (1) locomotor sensitization, (2) dopaminergic sensitization, and (3) escalated cocaine self-administration in rats. CRFR 1 antagonist CP376395 (50 or 500 ng/side), CRFR 2 antagonist Astressin 2 -B (100 or 1000 ng/side), or vehicle (aCSF) was microinjected into the VTA 20 min before social defeat stress (or handling) on days 1, 4, 7, and 10. Ten days later, rats were injected with cocaine (10 mg/kg, i.p.) and assessed for either locomotor sensitization, measured by walking activity, or dopaminergic sensitization, measured by extracellular dopamine (DA) in the nucleus accumbens shell (NAcSh) through in vivo microdialysis. Locomotor sensitization testing was followed by intravenous cocaine self-administration. Intra-VTA antagonism of CRFR 1 , but not CRFR 2 , inhibited the induction of locomotor cross-sensitization to cocaine, whereas both prevented dopaminergic cross-sensitization and escalated cocaine self-administration during a 24 h "binge." This may suggest dissociation between locomotor sensitization and cocaine taking. These data also suggest that interactions between CRF and VTA DA neurons projecting to the NAcSh are essential for the development of dopaminergic cross-sensitization to cocaine.

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In the setting of recalcitrant neuromas and intractable pain following multiple neuroma excisions, allografts may be suboptimal in reconstruction of larger gap defects. Autologous reconstruction with porcine submucosa extracellular matrix, as in this case, can avoid tethering, local ischemia, and nerve traction to optimize outcomes.

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