L A Knackstedt1, A Ettenberg. 1. Behavioral Pharmacology Laboratory, Department of Psychology, University of California, Santa Barbara, CA 93106, USA.
Abstract
RATIONALE: Human drug users report that the initial positive effects of cocaine are followed by a dysphoric state characterized by anxiety and drug-craving. As a means of presumably attenuating these negative aftereffects, 50-90% of cocaine users choose to co-administer ethanol during cocaine binges. This co-administration reportedly prolongs the "high" and diminishes the "low" associated with cocaine use. OBJECTIVE: The current study was intended to assess whether this phenomenon could be modeled in the animal laboratory. We have previously shown that animals running a straight alley for an intravenous cocaine reward develop a unique approach-avoidance "conflict" behavior that is characterized by stop and retreat behaviors as the subjects approach the goal box. The retreats are thought to reflect the concurrent positive (reward) and negative (anxiety) associations with the goal box and can be dose-dependently reduced by pretreatment with diazepam, which presumably attenuates the anxiety stemming from the conflict. METHODS: To test the role of ethanol in reducing cocaine-induced anxiety, rats were trained to run a straight-arm alley for a single daily injection of cocaine (1.0 mg/kg IV). RESULTS: Rats that had the opportunity to then drink either an 8% or a 4% sucrose-ethanol solution immediately following their daily runway trial came to exhibit fewer retreats than rats that did not drink ethanol following their cocaine injection. CONCLUSIONS: These results suggest that ethanol effectively reduces the development of approach-avoidance conflict in animals running an alley for IV cocaine, a result that may account for the prevalence of cocaine-ethanol co-administration in humans.
RATIONALE: Human drug users report that the initial positive effects of cocaine are followed by a dysphoric state characterized by anxiety and drug-craving. As a means of presumably attenuating these negative aftereffects, 50-90% of cocaine users choose to co-administer ethanol during cocaine binges. This co-administration reportedly prolongs the "high" and diminishes the "low" associated with cocaine use. OBJECTIVE: The current study was intended to assess whether this phenomenon could be modeled in the animal laboratory. We have previously shown that animals running a straight alley for an intravenous cocaine reward develop a unique approach-avoidance "conflict" behavior that is characterized by stop and retreat behaviors as the subjects approach the goal box. The retreats are thought to reflect the concurrent positive (reward) and negative (anxiety) associations with the goal box and can be dose-dependently reduced by pretreatment with diazepam, which presumably attenuates the anxiety stemming from the conflict. METHODS: To test the role of ethanol in reducing cocaine-induced anxiety, rats were trained to run a straight-arm alley for a single daily injection of cocaine (1.0 mg/kg IV). RESULTS:Rats that had the opportunity to then drink either an 8% or a 4% sucrose-ethanol solution immediately following their daily runway trial came to exhibit fewer retreats than rats that did not drink ethanol following their cocaine injection. CONCLUSIONS: These results suggest that ethanol effectively reduces the development of approach-avoidance conflict in animals running an alley for IV cocaine, a result that may account for the prevalence of cocaine-ethanol co-administration in humans.
Authors: E F McCance-Katz; L H Price; C J McDougle; T R Kosten; J E Black; P I Jatlow Journal: Psychopharmacology (Berl) Date: 1993 Impact factor: 4.530
Authors: Ami Cohen; Robert W Young; Miguel A Velazquez; Mariya Groysman; Kavon Noorbehesht; Osnat M Ben-Shahar; Aaron Ettenberg Journal: Psychopharmacology (Berl) Date: 2009-02-25 Impact factor: 4.530
Authors: Edmund A Griffin; Philippe A Melas; Royce Zhou; Yang Li; Peter Mercado; Kimberly A Kempadoo; Stacy Stephenson; Luca Colnaghi; Kathleen Taylor; Mei-Chen Hu; Eric R Kandel; Denise B Kandel Journal: Sci Adv Date: 2017-11-01 Impact factor: 14.136