title: Dopamine-induced plasticity, phospholipase D (PLD) activity and cocaine-cue behavior depend on PLD-linked metabotropic glutamate receptors in amygdala.
abstract: Cocaine-cue associations induce synaptic plasticity with long lasting molecular and cellular changes in the amygdala, a site crucial for cue-associated memory mechanisms. The underlying neuroadaptations can include marked alterations in signaling via dopamine (DA) receptors (DRs) and metabotropic glutamate (Glu) receptors (mGluRs). Previously, we reported that DR antagonists blocked forms of synaptic plasticity in amygdala slices of Sprague-Dawley rats withdrawn from repeated cocaine administration. In the present study, we investigated synaptic plasticity induced by exogenous DA and its dependence on mGluR signaling and a potential role for phospholipase D (PLD) as a downstream element linked to mGluR and DR signaling. Utilizing a modified conditioned place preference (CPP) paradigm as a functional behavioral measure, we studied the neurophysiological effects after two-weeks to the last cocaine conditioning. We recorded, electrophysiologically, a DR-induced synaptic potentiation in the basolateral to lateral capsula central amygdala (BLA-lcCeA) synaptic pathway that was blocked by antagonists of group I mGluRs, particularly, the PLD-linked mGluR. In addition, we observed 2-2.5 fold increase in PLD expression and 3.7-fold increase in basal PLD enzyme activity. The enhanced PLD activity could be further stimulated (9.3 fold) by a DA D1-like (D1/5R) receptor agonist, and decreased to control levels by mGluR1 and PLD-linked mGluR antagonists. Diminished CPP was observed by infusion of a PLD-linked mGluR antagonist, PCCG-13, in the amygdala 15 minutes prior to testing, two weeks after the last cocaine injection. These results imply a functional interaction between D1/5Rs, group I mGluRs via PLD in the amygdala synaptic plasticity associated with cocaine-cues.
authors: Department of Pharmacology and Toxicology, University of Texas Medical Branch at Galveston, Galveston, Texas, United States of America. bakrishn@utmb.edu
authors: Balaji
authors: B
authors: Krishnan
authors: Kathy M
authors: KM
authors: Genzer
authors: Sebastian W
authors: SW
authors: Pollandt
authors: Jie
authors: J
authors: Liu
authors: Joel P
authors: JP
authors: Gallagher
authors: Patricia
authors: P
authors: Shinnick-Gallagher
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003463:Cues; D003521:Cyclopropanes / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects*; D010739:Phospholipase D / Q000378:metabolism*; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D050641:Receptors, Dopamine D5 / Q000819:agonists / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C099854:2-(2'-carboxy-3'-phenylcyclopropyl)glycine; D001552:Benzazepines; D003521:Cyclopropanes; D007527:Isoenzymes; D017447:Receptors, Dopamine D1; D018094:Receptors, Metabotropic Glutamate; D050641:Receptors, Dopamine D5; D020891:Raclopride; D005680:gamma-Aminobutyric Acid; C067113:SK&F 81297; D010739:Phospholipase D; D003042:Cocaine; D005998:Glycine; D004298:Dopamine