Opposite effects of PCA and chlorimipramine on ICSS and on its facilitation by amphetamine

The long-term effects of chloramphetamine (PCA) and chlorimipramine (CHLOR) on intracranial self-stimulation (ICSS) were investigated in sessions lasting 13 h. PCA, 5 mg/kg given IP, led first to an attenuation of ICSS lasting 3 h, then to a slow recovery to baseline rates, and then to a facilitation of ICSS lasting 6 h. Repeating the treatment 7 days later resulted in less attenuation of ICSS, more rapid recovery, and longer-lasting facilitation. Again, repeating the treatment with PCA 7 days later but injecting simultaneously amphetamine (AMPH) 2 mg/kg IP, altered the response seen with PCA alone. The attenuation phase was missing but the facilitatory phase remained except that it occurred early and was of shorter duration than after PCA given alone. Pretreatment with haloperidol (HALO) 0.5 or 1.0 mg/kg IP before PCA blocked the facilitatory phase of the response. CHLOR injected at a dose of 15 mg/kg IP attenuated ICSS. The combined administration of CHLOR and AMPH led to the CHLOR-attenuation of ICSS being replaced by a modest facilitation. These results are discussed in terms of the biochemical actions of PCA and CHLOR on the serotonin and dopamine systems.