title: Intra-VTA deltorphin, but not DPDPE, induces place preference in ethanol-drinking rats: distinct DOR-1 and DOR-2 mechanisms control ethanol consumption and reward.
abstract: BACKGROUND
  While there is a growing body of evidence that the delta opioid receptor (DOR) modulates ethanol (EtOH) consumption, development of DOR-based medications is limited in part because there are 2 pharmacologically distinct DOR subtypes (DOR-1 and DOR-2) that can have opposing actions on behavior.
  
  
  METHODS
  We studied the behavioral influence of the DOR-1-selective agonist [D-Pen(2) ,D-Pen(5) ]-Enkephalin (DPDPE) and the DOR-2-selective agonist deltorphin microinjected into the ventral tegmental area (VTA) on EtOH consumption and conditioned place preference (CPP) and the physiological effects of these 2 DOR agonists on GABAergic synaptic transmission in VTA-containing brain slices from Lewis rats.
  
  
  RESULTS
  Neither deltorphin nor DPDPE induced a significant place preference in EtOH-naïve Lewis rats. However, deltorphin (but not DPDPE) induced a significant CPP in EtOH-drinking rats. In contrast to the previous finding that intra-VTA DOR-1 activity inhibits EtOH consumption and that this inhibition correlates with a DPDPE-induced inhibition of GABA release, here we found no effect of DOR-2 activity on EtOH consumption nor was there a correlation between level of drinking and deltorphin-induced change in GABAergic synaptic transmission.
  
  
  CONCLUSIONS
  These data indicate that the therapeutic potential of DOR agonists for alcohol abuse is through a selective action at the DOR-1 form of the receptor.
authors.affiliation: Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California; Department of Neurology, University of California, San Francisco, California.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Mitchell
authors.forename: Elyssa B
authors.initials: EB
authors.lastname: Margolis
authors.forename: Allison R
authors.initials: AR
authors.lastname: Coker
authors.forename: Daicia C
authors.initials: DC
authors.lastname: Allen
authors.forename: Howard L
authors.initials: HL
authors.lastname: Fields
mesh_terms: D000428:Alcohol Drinking / Q000523:psychology; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000008:administration & dosage*; D000431:Ethanol / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000502:physiology; D012201:Reward; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C059567:deltorphin; D000431:Ethanol; D020881:Enkephalin, D-Penicillamine (2,5)-
keywords: Delta Opioid Receptor; Ethanol; Place Preference; Reward; Self-Administration