title: Prior Exposure to Alcohol Has No Effect on Cocaine Self-Administration and Relapse in Rats: Evidence from a Rat Model that Does Not Support the Gateway Hypothesis.
abstract: The gateway hypothesis posits that initial exposure to legal drugs promotes subsequent addiction to illicit drugs. However, epidemiological studies are correlational and cannot rule out the alternative hypothesis of shared addiction vulnerability to legal and illegal drugs. We tested the gateway hypothesis using established rat alcohol exposure procedures and cocaine self-administration and reinstatement (relapse) procedures. We gave Wistar or alcohol-preferring (P) rats intermittent access to water or 20% alcohol in their homecage for 7 weeks (three 24-h sessions/week). We also exposed Wistar rats to air or intoxicating alcohol levels in vapor chambers for 14-h/day for 7 weeks. We then tested the groups of rats for acquisition of cocaine self-administration using ascending cocaine doses (0.125, 0.25, 0.5, 1.0 mg/kg/infusion) followed by a dose-response curve after acquisition of cocaine self-administration. We then extinguished lever pressing and tested the rats for reinstatement of drug seeking induced by cocaine-paired cues and cocaine priming (0, 2.5, 5, 10 mg/kg, i.p.). Wistar rats consumed moderate amounts of alcohol (4.6 g/kg/24 h), P rats consumed higher amounts of alcohol (7.6 g/kg/24 h), and Wistar rats exposed to alcohol vapor had a mean blood alcohol concentration of 176.2 mg/dl during the last week of alcohol exposure. Alcohol pre-exposure had no effect on cocaine self-administration, extinction responding, and reinstatement of drug seeking. Pre-exposure to moderate, high, or intoxicating levels of alcohol had no effect on cocaine self-administration and relapse to cocaine seeking. Our data do not support the notion that alcohol is a gateway drug to cocaine.
authors.affiliation: Cellular Neurobiology Branch, IRP-NIDA, NIH, Baltimore, MD, USA.|Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm, Sweden.
authors.forename: Ida
authors.initials: I
authors.lastname: Fredriksson
authors.affiliation: Behavioral Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA.
authors.forename: Sweta
authors.initials: S
authors.lastname: Adhikary
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm, Sweden.
authors.forename: Pia
authors.initials: P
authors.lastname: Steensland
authors.affiliation: Integrative Neuroscience Research Branch, IRP-NIDA NIH, Baltimore, MD, USA.
authors.forename: Leandro F
authors.initials: LF
authors.lastname: Vendruscolo
authors.affiliation: Cellular Neurobiology Branch, IRP-NIDA, NIH, Baltimore, MD, USA.|Solomon H. Snyder Neuroscience Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Antonello
authors.initials: A
authors.lastname: Bonci
authors.affiliation: Behavioral Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA.
authors.forename: Yavin
authors.initials: Y
authors.lastname: Shaham
authors.affiliation: Behavioral Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bossert
mesh_terms: D000818:Animals; D016739:Behavior, Addictive; D003042:Cocaine / Q000008:administration & dosage*; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage*; D005108:Extinction, Psychological / Q000187:drug effects; D023421:Models, Animal; D008960:Models, Psychological; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D012646:Self Administration
chemical_list: D000431:Ethanol; D003042:Cocaine