Prefrontal Cortical Regulation of Drug Seeking in Animal Models of Drug Relapse

Lasseter, Heather C.; Xie, Xiaohu; Ramirez, Donna R.; Fuchs, Rita A.

doi:10.1007/7854_2009_19

Cited by 58 publications

(68 citation statements)

References 79 publications

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“…Together these and the present findings are consistent with a circuitry model in which the BLA assesses the motivational significance of cocaine-paired CSs at the time of testing (Fuchs et al, 2002) based on input from the lOFC and VTA (See et al, 2001). The BLA may transmit the results of these computations to the PrL, which holds executive function (Lasseter et al, 2010) and integrates this information with input from the VTA (Ciccocioppo et al, 2001). Subsequently, the PrL mediates response selection and initiation via the NACc-dlVP circuit (Kalivas and McFarland, 2003).…”

Section: Conclusion: the Position Of The Lofc And Bla In The Cs-indusupporting

confidence: 89%

“…Thus, cueinduced relapse represents an enduring challenge for the successful treatment of cocaine addiction. Several brain regions have requisite roles in cocaine-seeking behavior produced by previously drug-paired conditioned stimuli (CS) in rodent models of cue-induced drug relapse (Bossert et al, 2013;Lasseter et al, 2010); however, few studies have aimed to identify functionally significant connections between these brain regions. As a result, our understanding of the neural circuitry by which drug-associated cues elicit motivation to seek cocaine is limited.…”

Section: Introductionmentioning

confidence: 99%

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Role of a Lateral Orbital Frontal Cortex-Basolateral Amygdala Circuit in Cue-Induced Cocaine-Seeking Behavior

Arguello

Richardson

Hall

et al. 2016

Neuropsychopharmacol

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Cocaine addiction is a disease characterized by chronic relapse despite long periods of abstinence. The lateral orbitofrontal cortex (lOFC) and basolateral amygdala (BLA) promote cocaine-seeking behavior in response to drug-associated conditioned stimuli (CS) and share dense reciprocal connections. Hence, we hypothesized that monosynaptic projections between these brain regions mediate CS-induced cocaine-seeking behavior. Male Sprague-Dawley rats received bilateral infusions of a Cre-dependent adeno-associated viral (AAV) vector expressing enhanced halorhodopsin 3.0 fused with a reporter protein (NpHR-mCherry) or a control AAV (mCherry) plus optic fiber implants into the lOFC (Experiment 1) or BLA (Experiment 2). The same rats also received bilateral infusions of a retrogradely transported AAV vector expressing Cre recombinase (Retro-Cre-GFP) into the BLA (Experiment 1) or lOFC (Experiment 2). Thus, NpHR-mCherry or mCherry expression was targeted to lOFC neurons that project to the BLA or to BLA neurons that project to the lOFC in different groups. Rats were trained to lever press for cocaine infusions paired with 5-s CS presentations. Responding was then extinguished. At test, response-contingent CS presentation was discretely coupled with optogenetic inhibition (5-s laser activation) or no optogenetic inhibition while lever responding was assessed without cocaine/food reinforcement. Optogenetic inhibition of lOFC to BLA, but not BLA to lOFC, projections in the NpHR-mCherry groups disrupted CS-induced reinstatement of cocaine-seeking behavior relative to (i) no optogenetic inhibition or (ii) manipulations in mCherry control or (iii) NpHR-mCherry food control groups. These findings suggest that the lOFC sends requisite input to the BLA, via monosynaptic connections, to promote CS-induced cocaine-seeking behavior.

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Section: Conclusion: the Position Of The Lofc And Bla In The Cs-indusupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Role of a Lateral Orbital Frontal Cortex-Basolateral Amygdala Circuit in Cue-Induced Cocaine-Seeking Behavior

Arguello

Richardson

Hall

et al. 2016

Neuropsychopharmacol

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“…Meth and mating coactivated neurons in the nucleus accumbens, basolateral amygdala, and the anterior cingulate area of the medial prefrontal cortex (Frohmader et al, 2010c) and in the orbitofrontal cortex (Frohmader and Coolen, 2010). The prefrontal and orbitofrontal cortices are of particular interest as they contribute to addictive behaviors Lasseter et al, 2010;Winstanley et al, 2010). Moreover, hypoactivity of these brain areas has been correlated with several psychiatric conditions associated with loss of inhibitory control (Graybiel and Rauch, 2000;Taylor et al, 2002;London et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Concurrent Exposure to Methamphetamine and Sexual Behavior Enhances Subsequent Drug Reward and Causes Compulsive Sexual Behavior in Male Rats

Frohmader¹,

Lehman²,

Laviolette³

et al. 2011

J. Neurosci.

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Methamphetamine (Meth) users report having heightened sexual pleasure, numerous sexual partners, and engaging in unprotected sex due to loss of inhibitory control. This compulsive sexual behavior contributes to increased prevalence of sexually transmitted infections, but the neural basis for this is unknown. We previously established a paradigm for compulsive sexual behavior in male rats in which visceral illness induced by lithium chloride was paired with sexual behavior (

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“…This same study further supported this hypothesis by demonstrating that glutamate AMPA/kainate receptor antagonism in the NAcc also inhibits discrete cue-induced heroin seeking. Although studies examining the putative role of the infralimbic cortex in cue-mediated drug seeking have been mixed (see Lasseter et al (2010a) for review), it appears that the lateral, but not medial, OFC is also involved in these types of drug-seeking behaviors, in that inactivation attenuates both discrete and contextual cue-induced cocaine seeking (Gallagher et al 1999;Fuchs et al 2004b;Lasseter et al 2009). …”

Section: Neurobiology Underlying Relapsementioning

confidence: 99%

Systems Level Neuroplasticity in Drug Addiction

Feltenstein

See

2013

Cold Spring Harbor Perspectives in Medicine

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Drug addiction is a chronic relapsing disorder for which research has been dedicated to understand the various factors that contribute to development, loss of control, and persistence of compulsive addictive behaviors. In this review, we provide a broad overview of various theories of addiction, drugs of abuse, and the neurobiology involved across the addiction cycle. Specific focus is devoted to the role of the mesolimbic pathway in acute drug reinforcement and occasional drug use, the mesocortical pathway and associated areas (e.g., the dorsal striatum) in escalation/dependence, and the involvement of these pathways and associated circuits in mediating conditioned responses, drug craving, and loss of behavioral control thought to underlie withdrawal and relapse. With a better understanding of the neurobiological factors that underlie drug addiction, continued preclinical and clinical research will aid in the development of novel therapeutic interventions that can serve as effective long-term treatment strategies for drug-dependent individuals.

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Prefrontal Cortical Regulation of Drug Seeking in Animal Models of Drug Relapse

Cited by 58 publications

References 79 publications

Role of a Lateral Orbital Frontal Cortex-Basolateral Amygdala Circuit in Cue-Induced Cocaine-Seeking Behavior

Role of a Lateral Orbital Frontal Cortex-Basolateral Amygdala Circuit in Cue-Induced Cocaine-Seeking Behavior

Concurrent Exposure to Methamphetamine and Sexual Behavior Enhances Subsequent Drug Reward and Causes Compulsive Sexual Behavior in Male Rats

Systems Level Neuroplasticity in Drug Addiction

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