title: Effects of protein kinase A inhibitor and activator on rewarding effects of SKF-82958 microinjected into nucleus accumbens shell of ad libitum fed and food-restricted rats.
abstract: BACKGROUND
  Previous studies indicate that the rewarding effect of D-1 dopamine receptor stimulation in nucleus accumbens (NAc) shell is greater in food-restricted (FR) than in ad libitum fed (AL) rats. The D-1 receptor is positively coupled to adenylyl cyclase and activates protein kinase A (PKA).
  
  
  OBJECTIVE
  The purpose of this study was to determine whether PKA is involved in the rewarding effect of D-1 receptor stimulation and, if so, whether it is involved in the enhanced response of FR rats.
  
  
  METHODS
  Rats were stereotaxically implanted with microinjection cannulae in NAc shell and a stimulating electrode in lateral hypothalamus. The rewarding effects of SKF-82958 (1.5 or 3.0 μg, bilaterally) in the presence and absence of PKA inhibitor, Rp-cAMPS (8.9 μg), and PKA activator, Sp-cAMPS (8.9 μg), were assessed using the curve-shift method of intracranial self-stimulation (ICSS). Basal NAc levels of DARPP-32 phosphorylated on Thr34 and Thr75 were measured.
  
  
  RESULTS
  Rp-cAMPS increased the rewarding effect of SKF-82958 in AL but not FR rats, doubling the ICSS threshold-lowering effect of the 3.0-μg dose. Sp-cAMPS decreased the rewarding effect of SKF-82958 in FR but not AL rats. Levels of phospho-DARPP-32 (Thr75), which inhibits PKA, were higher in FR than AL rats.
  
  
  CONCLUSIONS
  Results indicate that inhibition of PKA enhances the unconditioned rewarding effect of D-1 receptor stimulation and that decreased PKA may be involved in the effect of FR on drug reward. Evidence for involvement of D-2 receptor-expressing neurons in the enhancing effect of PKA inhibition is discussed.
authors.affiliation: Department of Psychiatry, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Soledad Cabeza
authors.initials: SC
authors.lastname: de Vaca
authors.forename: Xing-Xiang
authors.initials: XX
authors.lastname: Peng
authors.forename: Seth
authors.initials: S
authors.lastname: Concors
authors.forename: Casey
authors.initials: C
authors.lastname: Farin
authors.forename: Elena
authors.initials: E
authors.lastname: Lascu
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Carr
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005508:Food Deprivation; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D012201:Reward; D012653:Self Stimulation; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D047428:Protein Kinase Inhibitors; D017447:Receptors, Dopamine D1; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; C071262:SK&F 82958; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases