Get access

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

Authors

  • Jennifer M. Mitchell,

    Corresponding author
    1. Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California
    2. Department of Neurology, University of California, San Francisco, California
    • Reprint requests: Jennifer M. Mitchell, PhD, Ernest Gallo Clinic and Research Center, 5858 Horton Street, Suite #200, Emeryville, CA 94608; Tel.: 510-985-3921; Fax: 510-985-3101; E-mail: jennifer.mitchell@ucsf.edu

    Search for more papers by this author
  • Elyssa B. Margolis,

    1. Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California
    2. Department of Neurology, University of California, San Francisco, California
    Search for more papers by this author
  • Allison R. Coker,

    1. Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California
    2. Department of Neurology, University of California, San Francisco, California
    Search for more papers by this author
  • Daicia C. Allen,

    1. Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California
    Search for more papers by this author
  • Howard L. Fields

    1. Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California
    2. Department of Neurology, University of California, San Francisco, California
    Search for more papers by this author

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-Pen2,D-Pen5]-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.

Get access to the full text of this article

Ancillary