title: Ibotenic acid lesions of the medial prefrontal cortex block the development and expression of 3,4-methylenedioxymethamphetamine-induced behavioral sensitization in rats.
abstract: There is ample evidence that plastic changes in the nervous system require the excitatory amino acid transmission. This appears to be also the case for psychostimulant-induced behavioral sensitization. More specifically the glutamatergic input from the medial prefrontal cortex (mPFC) to the VTA and the NAc appears to be involved in behavioral sensitization processes. However, dissociations regarding the role of the mPFC with respect to the development and expression of sensitization, as well as with respect to the psychostimulant being studied (amphetamine versus cocaine) appear to exist. The present study examined the role of the dorsal mPFC in the development and expression of 3,4-methylenedioxymethamphetamine (MDMA)-induced sensitization. Bilateral ibotenic acid or sham lesions of the dorsal mPFC were performed 7 days prior to or 4 days after a context-dependent sensitization-inducing regimen of MDMA (15 mg/kg i.p.) or saline. Rats were then challenged with MDMA (5 mg/kg i.p.) after 12 days of withdrawal. Ibotenic acid lesions did not affect the activating effects of MDMA, but prevented the development and expression of MDMA sensitization. Thus, the distance traveled during the development phase of sensitization increased in sham-lesioned rats but not in ibotenic-lesioned animals. Similarly, sham-lesioned rats showed a sensitized response when challenged with MDMA after the withdrawal period, an effect not observed in ibotenic-lesioned animals. These data reinforce the view that the dorsal mPFC is involved in psychostimulant sensitization and more specifically they indicate that the dorsal mPFC plays a key role in the development and expression of MDMA-induced behavioral sensitization.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Navarra, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Ramos
authors.forename: Beatriz
authors.initials: B
authors.lastname: Goñi-Allo
authors.forename: Norberto
authors.initials: N
authors.lastname: Aguirre
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001927:Brain Diseases / Q000503:physiopathology; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007051:Ibotenic Acid / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects; D017397:Prefrontal Cortex / Q000293:injuries / Q000473:pathology / Q000502:physiology*; D051381:Rats; D013997:Time Factors
chemical_list: D018759:Adrenergic Uptake Inhibitors; D018690:Excitatory Amino Acid Agonists; D007051:Ibotenic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine