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HMB200H1 Study Guide - Anterior Cingulate Cortex, Prefrontal Cortex, Functional Magnetic Resonance Imaging

Human Biology
Course Code
Uwe Erb

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DUPE AINA 997536527
The Role Of The Prefrontal Cortex In The Reinstatement of Drug Use And Its Relevance
To Incubation Of Drug Craving
This review paper explores recent finding on the role of the prefrontal cortex
(PFC) in the incubation of drug craving and reinstatement. It looks into the individual
role played by the anterior cingulate cortex (ACC), orbitofrontal Cortex (OFC), ventral
medial prefrontal cortex (ventral mPFC) and dorsal medial prefrontal cortex (dorsal
mPFC); regions highly implicated in drug addiction. The first sections looks into recent
findings on the role of the OFC and ACC in cue induced reinstatement and incubation of
craving. In subsequent sections the ventral mPFC is implicated in reinstatement and
incubation with studies that suggest a higher activity in this region than other regions of
the PFC. Finally this review is brought to a close with concluding remarks that suggest
the neural circuitries involved in reinstatement and incubation are more extensive and
might include other regions beyond the PFC.
A rapid transition from recreational to regular patterns of drug use is considered
an important prognosticator of whether an individual will later develop problems with
substance abuse and dependence. (Smith, 2011). Consequently, one of the goals of
substance abuse prevention programs is to discourage the development of regular patterns
of drug use and relapse in at-risk populations. (Smith, 2011). Reinstatement is the
acquisition of regular patterns of drug intake after initial drug exposure. (Smith, 2011).
The reinstatement model is currently used in many laboratories to investigate
mechanisms underlying relapse to drug seeking. (Shaham et al., 2003). Reinstatement can

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DUPE AINA 997536527
be modeled in the laboratory using either of two behavioral procedures; self-
administration, and conditioned place preference (CPP). Both models are characterized
by a training phase where a behavior is reinforced by contingent pairing with access to
drug. This is followed by the extinction phase where extinction of the drug-reinforced
behavior occurs. The animal is then tested for reinstatement of drug seeking after
extinction. (Shaham et al., 2003). Factors that influence the reinstatement of drug seeking
in laboratory animals are often identical to the factors that influence the likelihood an
individual will develop problems with substance use and dependence. For instance, social
isolation or change in context (context-induced reinstatement), stress (stress-induced
reinstatement), previous drug exposure (primed or drug induced reinstatement) and drug-
associated stimuli (cue-induced reinstatement) increase the rate of reinstatement of drug
use in laboratory animals and are considered risk factors for relapse in humans with
substance dependence. (Smith, 2011).
Prefrontal cortex (PFC) Anatomy
In this review general definitions described for both rodents and primates by Price
(2007) will be used. The extent to which region specific neurobehavioral processes are
similar across species is controversial, primarily because prefrontal cortex (PFC) shows
species-specific variation in size relative to other cortical areas (encephalization),
anatomical cytoarchitecture, neurochemistry and connectivity. (Perry et al., 2011). Rather
than emphasizing cross-species differences, this review instead will use common
nomenclature where possible to allow for generalizing behavioral results across rodents
and primates. (Perry et al., 2011). Price (2007) differentiates between two major PFC

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DUPE AINA 997536527
networks: the medial, and the orbital networks. The medial prefrontal cortex (mPFC)
often refers to various structures located along the medial wall of PFC. (Price, 2007). The
precentral cortex (PrC) and anterior cingulate cortex (ACC) together are often referred to
as dorsal mPFC, whereas the prelimbic (PrL), infralimbic (IL), medial orbital (MO), and
ventral orbital (VO) cortices together are referred to as ventral medial prefrontal cortex
(ventral mPFC). We are now going to explore these brain regions individually in relation
to their effects on reinstatement and incubation of drug craving.
Anterior Cingulate Cortex (ACC) and Orbitofrontal Cortex (OFC)
Addiction is increasingly considered to involve maladaptation in the ACC and
OFC. These regions are known to influence cognitive function related to goal-directed
behavior, and are particularly reactive to drug cues in humans and animals. (Goldstein et
al., 2009). In a study conducted by Gremel et al. (2011) CPP procedure was used to test
for reinstatement. It consisted of 3 phases: conditioning, extinction and testing as outlined
above. An opioid receptor antagonist methylnaloxonium was infused into the ACC
immediately before the testing phase where the expression of cue-induced ethanol CPP
was assessed. It was observed that the blockage of opioid receptors in the ACC reduced
cue-induced ethanol-seeking behavior in mice. In another study by Li et al. (2012)
neuroimaging techniques were used to explore regional brain activations associated with
craving during the presentation of smoking-related cues. ACC activity was observed in
response to cigarette cues and real-time functional magnetic resonance imaging (rtfMRI)
neurofeedback was applied to improve their ability to reduce their neural and subjective
craving response to smoking cues. Using rtfMRI, nicotine-dependent cigarette smokers
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