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Review
. 2016 Jul:91:326-35.
doi: 10.1016/j.nbd.2016.02.021. Epub 2016 Feb 26.

Prefrontal cortical BDNF: A regulatory key in cocaine- and food-reinforced behaviors

Elizabeth G Pitts  1 , Jane R Taylor  2 , Shannon L Gourley  3
Affiliations
Review

Prefrontal cortical BDNF: A regulatory key in cocaine- and food-reinforced behaviors

Elizabeth G Pitts et al. Neurobiol Dis. 2016 Jul.

Abstract

Brain-derived neurotrophic factor (BDNF) affects synaptic plasticity and neural structure and plays key roles in learning and memory processes. Recent evidence also points to important, yet complex, roles for BDNF in rodent models of cocaine abuse and addiction. Here we examine the role of prefrontal cortical (PFC) BDNF in reward-related decision making and behavioral sensitivity to, and responding for, cocaine. We focus on BDNF within the medial and orbital PFC, its regulation by cocaine during early postnatal development and in adulthood, and how BDNF in turn influences responding for drug reinforcement, including in reinstatement models. When relevant, we draw comparisons and contrasts with experiments using natural (food) reinforcers. We also summarize findings supporting, or refuting, the possibility that BDNF in the medial and orbital PFC regulate the development and maintenance of stimulus-response habits. Further investigation could assist in the development of novel treatment approaches for cocaine use disorders.

Keywords: Addiction; Goal-directed; Instrumental; Operant; Orbitofrontal; Prelimbic; Review.

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Conflict of interest statement

The authors report no conflicts of interest.

Figures

Figure 1
Figure 1. Regions of the rodent prefrontal cortex
The mouse PFC can be divided into the anterior cingulate cortex (green), PL (gray), IL (purple), medial oPFC (yellow), ventrolateral oPFC (blue), and lateral oPFC (orange). The agranular insula, often studied in concert with the lateral oPFC, is lateral to the lateral oPFC. Regions outlined on coronal images from the Mouse Brain Library (Rosen et al., 2000).
Figure 2
Figure 2. PL BDNF regulates responding for “natural reward”
(a) Viral vectors expressing Cre Recombinase were delivered to the PL of ‘floxed’ Bdnf mice, generating a site-selective knockdown. Control mice received a viral vector expressing Green Fluorescent Protein (GFP). The largest viral vector spread is represented in gray, the smallest in black. (b) Bdnf knockdown caused a persistent drop in responding for food reinforcers on a progressive ratio schedule of reinforcement; meanwhile, knockdown increases cocaine-reinforced responding on a progressive ratio schedule (Sadri-Vakili et al., 2010). (c) We re-analyzed data from typical mice or mice chronically exposed to the stress hormone corticosterone in Gourley et al. (2012a), generating groups based on a median split of endogenous PL BDNF levels. Corticosterone reduced BDNF overall. Additionally, “high” BDNF was associated with high break point ratios, while “low” BDNF was associated with low break point ratios, again pointing to differential roles for mPFC BDNF in regulating food- vs. cocaine-reinforced responding on a progressive ratio schedule (cf., Sadri-Vakili et al., 2010). Figure components are compiled or reprinted from Gourley et al., 2012a. Bars and symbols represent group means+SEMs, *p<0.05.
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