Does the PCPA induced anticonflict effect involve activation of the GABAA/benzodiazepine chloride ionophore receptor complex?

The effects of the benzodiazepine (BDZ) receptor antagonist flumazenil (Ro 15-1788) and the GABAA receptor antagonist bicuculline on the anticonflict effect observed after depletion of brain serotonin (5-HT), were examined in a modified Vogel's punished drinking conflict model. Pretreatment with para-chlorophenylalanine (PCPA; 300 mg/kg/day for three days, last injection - 24 h) markedly decreased brain 5-HT levels and produced clearcut anticonflict effects. The anticonflict effect, but not the biochemical effect, of PCPA pretreatment was completely counteracted by both flumazenil (10 mg/kg, - 30 min) and bicuculline (2.0 mg/kg, - 10 min), in doses not altering the behavior per se. The findings suggest a behavioral interaction between 5-HT systems and the GABAA/BDZ chloride ionophore receptor complex, possibly involving a direct neuronal interaction, neuromodulation or hormonal alterations.