Behavioral sensitization produced by a single administration of apomorphine: implications for the role of Pavlovian conditioning in the mediation of context-specific sensitization.

The present study examined the minimal number of exposures to the D1/D2 agonist apomorphine capable of producing behavioral sensitization. Rats received one (experiment 1) or two administrations on two successive days (experiment 2) of apomorphine (0.5 and 2.0 mg/kg) paired or unpaired to an open-field environment. After 2 days of drug withdrawal, the rats received a challenge injection with the same dose of apomorphine (sensitization test) and locomotion, rearing and sniffing were measured. The results of the first experiment showed that locomotor sensitization occurred after a single acute exposure to apomorphine and that 0.5 and 2.0 mg/kg treatments were equally effective. This sensitization effect was context-specific and was limited to locomotion. The second experiment revealed a differential dose effect on the sensitization test. Two treatments with 2.0 mg/kg potentiated locomotor sensitization as compared with a single treatment but two treatments with 0.5 mg/kg did not increase the sensitization effect more than the single 0.5 mg/kg treatment. This result indicates an interaction between drug dose and frequency of drug treatment for the induction of apomorphine locomotor sensitization. In that the sensitization effects are considered to be a core contributor to psychostimulant addiction, the present findings are of importance to understanding addiction because they indicate that sensitization processes can be initiated with a single drug experience and amplified with exposure to higher drug dosage levels.