Effect of a dopamine D1/5 receptor antagonist on haloperidol-induced inhibition of the acquisition of conditioned fear.
This study examined the effects of combined treatment with the typical antipsychotic drug haloperidol and dopamine D1/5 receptor antagonist SCH 23390 on the acquisition of contextual conditioned fear (re-exposure to an environment paired previously with inescapable electric footshocks), compared with those of various antipsychotic adjuvants, which may increase the effects of antipsychotic drugs. Rats were treated subcutaneously with haloperidol (3 mg/kg) combined with SCH 23390 (0.03 mg/kg) and were given fear conditioning by 5 min footshocks in shock chambers 30 min after the injection. One week after the footshocks, the rats were tested in the same shock chamber without shocks and freezing behavior was observed as an index of fear and anxiety. Haloperidol significantly inhibited the acquisition of conditioned freezing. SCH 23390 combined with haloperidol inhibited the acquisition of conditioned freezing more than either drug alone did. These results suggest that combined dopamine D2-like receptor antagonism and dopamine D1-like receptor antagonism is a promising and effective strategy to increase antipsychotic effects.
Inoue
Takeshi
T
Department of Psychiatry, Neural Function, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan. tinoue@med.hokudai.ac.jp
Izumi
Takeshi
T
Li
Xiao Bai
XB
Kitaichi
Yuji
Y
Nakagawa
Shin
S
Koyama
Tsukasa
T
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects* / Q000523:psychology; D006220:Haloperidol / Q000494:pharmacology*; D016651:Lithium Carbonate / Q000494:pharmacology; D008297:Male; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D050641:Receptors, Dopamine D5; D012702:Serotonin Antagonists / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; C493607:Drd5 protein, rat; D011804:Quinolines; D017447:Receptors, Dopamine D1; D012702:Serotonin Antagonists; D050641:Receptors, Dopamine D5; D016651:Lithium Carbonate; C054363:2-((2-(dimethylamino)ethyl)thio)-3-phenylquinoline; D006220:Haloperidol