Second-order (environmental) conditioning of a taste aversion in rats

Four groups of rats (n=10/group) were conditioned in a taste aversion task using a second-order reinforcer associated with precipitated morphine withdrawal. Rats in CS+, CS- and CS(random) groups were exposed to a chronic morphine (morphine sulfate, MS) dosing regimen. A control group received equivalent volumes of saline. All rats then received daily i.p. injections of naloxone HCl (1.0-3.2 mg/kg), inducing precipitated morphine withdrawal in group-dependent unique environments. The 4-h withdrawal trials were terminated by a 20 mg/kg MS injection (MS treatment groups only) and returned to their home cage. After a 1-week wash-out was imposed, all subjects were exposed to a conditioned taste aversion (CTA) task using environmental stimuli (CS1) from Phase 1 paired with saccharin (CS2) in a second-order conditioning procedure. The CS+ group developed a significant CTA; the CS- and CS(random) groups increased their consumption of saccharin. The saline group was unaffected by the treatment conditions. The data demonstrate the salience and importance of environmental stimuli and suggest a role for such conditioning in drug relapse phenomena.