Norepinephrine in prelimbic cortex delays extinction of amphetamine-induced conditioned place preference

• Published in: Psychopharmacology 2016-03, Vol.233 (6), p.973-982
• Main Authors: Latagliata, Emanuele Claudio, Saccoccio, Pamela, Milia, Chiara, Puglisi-Allegra, Stefano
• Format: Article
• Language: English
• Subjects: Amphetamine - pharmacology; Amphetamines; Animal behavior; Animals; Association Learning - drug effects; Biomedical and Life Sciences; Biomedicine; Cues; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Dosage and administration; Drug addiction; Drug interactions; Drug-Seeking Behavior - drug effects; Health aspects; Male; Mice; Mice, Inbred C57BL; Neocortex; Neurosciences; Neurotransmitters; Norepinephrine; Norepinephrine - metabolism; Observations; Original Investigation; Oxidopamine - toxicity; Pharmacology/Toxicology; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Psychiatry; Psychopharmacology; Rodents
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-015-4177-6

Rationale Drug-associated cues exposure to induce extinction is a useful strategy to contrast cue-induced drug seeking. Treatments aimed at reducing motivational properties of cues are considered highly promising since they could decrease their ability to induce drug-conditioned behaviors. Norepinephrine (NE) in the medial prefrontal cortex (mPFC) is critical for attribution of motivational salience to highly salient stimuli, suggesting a major role in prelimbic (PL) mpFC to modulate the motivational properties of drug-related cues, invigorating them, and consequently, delaying extinction. Objectives To investigate if NE in PL fosters the maintenance of drug-seeking behavior, we assessed its role on amphetamine-induced conditioned place preference (CPP). Moreover, to affirm the specificity of NE in PL, we also assessed the role of NE in the infralimbic (IL) mPFC. Methods The effects of selective NE depletion in the PL or in the IL of C57BL/6J mice were assessed on the expression of amphetamine-induced CPP before and after extinction procedure. Results NE-depleted mice in PL extinguished preference for Amph-paired chamber long before sham animals. By contrast, IL-depleted animals maintained place preference for more than 4 weeks after the procedure of extinction, having at that moment interrupted the test. Conclusions Inactivation of NE in PL cortex blunts amphetamine-induced CPP, thus fostering extinction and showing to be critical for the maintenance of conditioned Amph-seeking behavior. Opposite effects of NE depletion in IL, seemingly in agreement with literature on extinction, are discussed in terms of balance of activity between PL and IL in extinction.