Food-induced behavioral sensitization, its cross-sensitization to cocaine and morphine, pharmacological blockade, and effect on food intake

Repeated administration of abused drugs sensitizes their stimulant effects and results in a drug-paired environment eliciting conditioned activity. We tested whether food induces similar effects. Food-deprived male mice were given novel food during 30 min tests in a runway (FR group) that measured locomotor activity. Whereas the activity of this group increased with repeated testing, that of a group exposed to the runways but that received the food in the home cage (FH group), or of a group satiated by prefeeding before testing ( SAT group), decreased. When exposed to the runways in the absence of food, the paired group was more active than the other groups ( conditioned activity); no activity differences were seen in an alternative, non-food-paired, apparatus. Conditioned activity survived a 3-week period without runway exposure. Conditioned activity was selectively reduced by the opiate antagonist naltrexone (10-20 mg/kg) and by the noncompetitive AMPA receptor antagonist GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride] (5-10 mg/ kg). The D-1 antagonist SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride] (15-30 mu g/kg) and D-2 antagonist sulpiride (25-125 mg/kg) reduced activity nonspecifically. A single intraperitoneal dose of cocaine (10 mg/ kg) or morphine ( 20 mg/ kg) increased activity compared with saline, the stimulant effect being larger in the FR group, suggesting "cross-sensitization" to these drugs. However, pretreatment with GYKI 52466 or naltrexone at doses that suppressed conditioned activity in FR animals suppressed cross-sensitization to cocaine. When allowed ad libitum access to food in the runway, FR mice consumed more pellets in a time-limited test. Thus, many of the features of behavioral sensitization to drugs can be demonstrated using food reward and may contribute to excessive eating.