Cholecystokinin modulates both the development and the expression of behavioral sensitization to amphetamine in the rat

Rationale: Repeated administration of psychostimulants such as amphetamine (AMPH) produces an enduring augmentation of their locomotor effects. Previo us research suggests that this phenomenon, termed sensitization, is related to changes within the mesolimbic dopamine (DA) system. Objectives: The pre sent experiments were designed to investigate the contribution of endogenou s cholecystokinin (CCK), a neuropeptide co-localized with DA in the mesolim bic system, to the development (experiment 1) and the expression (experimen t 2) of locomotor sensitization to AMPH. Methods: In experiment 1, rats wer e injected (IP) with the CCKA antagonist devazepide (0, 0.001, 0.01, or 0.1 mg/kg) or the CCKB antagonist L-365,260 (0, 0.001, 0.01, 0.1, or 1.0 mg/kg ) followed by AMPH (1.5 mg/kg) once daily for seven days. Following 10 days withdrawal, rats were administered AMPH (0.75 mg/kg) and their locomotor a ctivity recorded. In experiment 2, rats were administered AMPH (1.5 mg/kg) once daily for 7 days. Following 10 days withdrawal, rats were injected wit h devazepide (0, 0.0001, 0.001, 0.01, 0.1, or 1.0 mg/kg) or L-365,260 (0, 0 .001, 0.01, or 0.1 mg/kg;) followed 30 min later by AMPH (0.75 mg/kg) and t heir locomotor activity recorded. Results: When administered during the AMP H pretreatment phase of experiment 1, the two highest doses of L-365,260 at tenuated, and the lowest dose of L-365,260 potentiated, the sensitized loco motor response to AMPH challenge. When administered prior to the AMPH chall enge phase of experiment 2, devazepide attenuated the sensitized locomotor response to AMPH. Conclusions: These results suggest that CCKB and CCKA rec eptors modulate the development and the expression of behavioral sensitizat ion to AMPH, respectively.