SYMMETRICAL EFFECTS OF AMPHETAMINE AND ALPHA-FLUPENTIXOL ON CONDITIONED PUNISHMENT AND CONDITIONED REINFORCEMENT - CONTRASTS WITH MIDAZOLAM

In a test of conditioned punishment, saline-treated controls showed a moderate bias in responding away from a lever producing a response-con tingent auditory conditioned stimulus (CS) that had been paired with m ild footshock during training and towards a lever producing a neutral auditory CS. Systemic treatment with the indirect dopamine (DA) agonis t amphetamine (0.25-1.0 mg/kg) produced a dose-dependent increase in t he punishing effect of the aversive CS, whilst responding on the neutr al CS lever was unchanged. Treatment with the dopamine-receptor antago nist alpha-flupenthixol (0.125, 0.25 mg/kg) decreased the efficacy of the punishing CS, but again left responding on the neutral lever uncha nged. The benzodiazepine midazolam (0.1, 0.3 mg/kg) had a similar effe ct to alpha-flupenthixol, but treated animals showed a preference for the aversive CS. Parallel results were observed with amphetamine (0.25 mg/kg) and alpha-flupenthixol (0.125, 0.25 mg/kg) in a matched test o f positive conditioned reinforcement, with amphetamine enhancing, and alpha-flupenthixol reducing, the efficacy of the CS paired with food. Midazolam treatment (0.1-1.0 mg/kg) had no effect on the reinforcing i mpact of an appetitive CS. Thus dopaminergic agents modulate the behav ioural impact of both appetitively and aversively motivated conditione d stimuli on instrumental performance, whilst the benzodiazepine midaz olam has a selective impact on aversively-motivated stimuli that is qu alitatively distinct from that of the dopaminergic antagonist alpha-fl upenthixol.