TY - JOUR
T1 - Does Antagonism at 5-HT 2A Receptors Potentiate D2 Blockade-Induced Disruption of Conditioned Avoidance Response?
AU - Gao, Jun
AU - Huang, Yujing
AU - Li, Ming
N1 - Funding Information:
This research was supported by a grant from the National Natural Science Foundation of China (31500891 to Jun Gao); the Fundamental Research Funds for the Central Universities (SWU1609131 and SWU115030 to Jun Gao and SWU116014 to Ming Li); the Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology (KLMH2016G03 to Jun Gao); and Chongqing Collaborative Innovation Center for Brain Science, China (Ming Li). The funding source had no role other than financial support. Ming Li and Jun Gao designed and supervised all experiments and also contributed to the writing and editing of the manuscript. Jun Gao and Yujing Huang conducted the experiments and data analysis and wrote the first draft of this article. All authors have read and approved the final manuscript. Jun Gao and Yujing Huang contributed equally to this work.
Publisher Copyright:
© 2018 American Psychological Association.
PY - 2019/4
Y1 - 2019/4
N2 - Existing evidence in the literature shows that antagonism at 5-HT 2A receptors potentiates D2 antagonisminduced disruption of conditioned avoidance response (CAR), a behavioral index of antipsychotic activity, suggesting that combining 5-HT 2A antagonism with D2 antagonism may confer an enhanced antipsychotic effect. The present study reexamined this issue and further investigated other behavioral effects of drug- drug interaction, mainly the conditioned drug effect (via drug- drug conditioning) and 5-HT 2A antagonism's modulation on antipsychotic-induced sensitization (an enhanced avoidance disruption). Well-trained adult male Sprague-Dawley rats were first repeatedly tested for 7 days under haloperidol (HAL; 0.05 mg/kg, subcutaneous [sc], a typical antipsychotic drug with potent D2 antagonism), MDL100907 (0.5 and 1.0 mg/kg, sc, a selective 5-HT 2A antagonist), combined MDL100907 and HAL, or vehicle control, followed by one challenge test under MDL100907 (0.5 mg/kg) to assess the conditioned drug effect and one challenge test under HAL (0.025 mg/kg) to assess HAL sensitization. Results showed that MDL100907 by itself had no effect on CAR. Importantly, MDL100907 treatment did little to alter the acute and sensitized effects of HAL-induced (0.05 mg/kg, sc) suppression of CAR under various treatment conditions. Repeated pairing of MDL100907 (1.0 mg/kg) with HAL rendered MDL100907 itself to exhibit an "acquired" CAR disruptive effect through a drug- drug conditioning process. These results do not support the notion that 5-HT 2A receptor blockade enhances the antipsychotic-like effects of typical antipsychotic drugs, although they do highlight the importance of drug- drug conditioning process in altering drug efficacy in polypharmacy.
AB - Existing evidence in the literature shows that antagonism at 5-HT 2A receptors potentiates D2 antagonisminduced disruption of conditioned avoidance response (CAR), a behavioral index of antipsychotic activity, suggesting that combining 5-HT 2A antagonism with D2 antagonism may confer an enhanced antipsychotic effect. The present study reexamined this issue and further investigated other behavioral effects of drug- drug interaction, mainly the conditioned drug effect (via drug- drug conditioning) and 5-HT 2A antagonism's modulation on antipsychotic-induced sensitization (an enhanced avoidance disruption). Well-trained adult male Sprague-Dawley rats were first repeatedly tested for 7 days under haloperidol (HAL; 0.05 mg/kg, subcutaneous [sc], a typical antipsychotic drug with potent D2 antagonism), MDL100907 (0.5 and 1.0 mg/kg, sc, a selective 5-HT 2A antagonist), combined MDL100907 and HAL, or vehicle control, followed by one challenge test under MDL100907 (0.5 mg/kg) to assess the conditioned drug effect and one challenge test under HAL (0.025 mg/kg) to assess HAL sensitization. Results showed that MDL100907 by itself had no effect on CAR. Importantly, MDL100907 treatment did little to alter the acute and sensitized effects of HAL-induced (0.05 mg/kg, sc) suppression of CAR under various treatment conditions. Repeated pairing of MDL100907 (1.0 mg/kg) with HAL rendered MDL100907 itself to exhibit an "acquired" CAR disruptive effect through a drug- drug conditioning process. These results do not support the notion that 5-HT 2A receptor blockade enhances the antipsychotic-like effects of typical antipsychotic drugs, although they do highlight the importance of drug- drug conditioning process in altering drug efficacy in polypharmacy.
KW - Conditioned avoidance response
KW - Drug-drug conditioning
KW - Haloperidol
KW - MDL100907
KW - Schizophrenia
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U2 - 10.1037/pha0000243
DO - 10.1037/pha0000243
M3 - Article
C2 - 30556732
AN - SCOPUS:85058848326
SN - 1064-1297
VL - 27
SP - 103
EP - 108
JO - Experimental and Clinical Psychopharmacology
JF - Experimental and Clinical Psychopharmacology
IS - 2
ER -