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.
Söderpalm
B
B
Department of Pharmacology, University of Göteborg, Sweden.
Engel
J A
JA
D000818:Animals; D001007:Anxiety / Q000187:drug effects*; D001640:Bicuculline / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D010134:Fenclonine / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism
D011963:Receptors, GABA-A; D012701:Serotonin; D005442:Flumazenil; D010134:Fenclonine; D009638:Norepinephrine; D001640:Bicuculline