TY - JOUR
T1 - The receptor mechanisms underlying the disruptive effects of haloperidol and clozapine on rat maternal behavior
T2 - A double dissociation between dopamine D2 and 5-HT2A/2C receptors
AU - Zhao, Changjiu
AU - Li, Ming
N1 - Funding Information:
This research was supported by a grant from the National Institute of Mental Health (5R03MH080822-02). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. We would like to thank Wei He for his administrative and technical help with this work.
PY - 2009/10
Y1 - 2009/10
N2 - Many antipsychotic drugs disrupt active components of maternal behavior such as pup approach, pup retrieval and nest building at clinically relevant doses in postpartum female rats. However, the neurochemical mechanisms underlying such a disruptive effect remain to be determined. This study examined the neurochemical mechanisms that mediate the disruptive effects of haloperidol (a typical antipsychotic) and clozapine (an atypical antipsychotic) on rat maternal behavior. Postpartum rats were administered with haloperidol (0.2 mg/kg, sc) or clozapine (10.0 mg/kg, sc) together with either vehicle (saline or water), quinpirole (a selective dopamine D2/D3 agonist, 0.5 or 1.0 mg/kg, sc), or 2,5-dimethoxy-4-iodo-amphetamine (DOI, a selective 5-HT2A/2C agonist, 1.0 or 2.5 mg/kg, sc), and their maternal behaviors were tested at different time points before and after drug administration. Haloperidol and clozapine treatment disrupted pup approach, pup retrieval, pup licking and nest building. Pretreatment of quinpirole, but not DOI, dose-dependently reversed the haloperidol-induced disruptions. In contrast, pretreatment of DOI, but not quinpirole, dose-dependently reversed the clozapine-induced disruptions. Quinpirole pretreatment even exacerbated the clozapine-induced disruption of pup retrieval and nest building. These findings suggest a double dissociation mechanism underlying the disruption of haloperidol and clozapine on rat maternal behavior. Specifically, haloperidol disrupts maternal behavior primarily by blocking dopamine D2 receptors, whereas clozapine exerts its disruptive effect primarily by blocking the 5-HT2A/2C receptors. Our findings also suggest that 5-HT receptors are involved in the mediation of rat maternal behavior.
AB - Many antipsychotic drugs disrupt active components of maternal behavior such as pup approach, pup retrieval and nest building at clinically relevant doses in postpartum female rats. However, the neurochemical mechanisms underlying such a disruptive effect remain to be determined. This study examined the neurochemical mechanisms that mediate the disruptive effects of haloperidol (a typical antipsychotic) and clozapine (an atypical antipsychotic) on rat maternal behavior. Postpartum rats were administered with haloperidol (0.2 mg/kg, sc) or clozapine (10.0 mg/kg, sc) together with either vehicle (saline or water), quinpirole (a selective dopamine D2/D3 agonist, 0.5 or 1.0 mg/kg, sc), or 2,5-dimethoxy-4-iodo-amphetamine (DOI, a selective 5-HT2A/2C agonist, 1.0 or 2.5 mg/kg, sc), and their maternal behaviors were tested at different time points before and after drug administration. Haloperidol and clozapine treatment disrupted pup approach, pup retrieval, pup licking and nest building. Pretreatment of quinpirole, but not DOI, dose-dependently reversed the haloperidol-induced disruptions. In contrast, pretreatment of DOI, but not quinpirole, dose-dependently reversed the clozapine-induced disruptions. Quinpirole pretreatment even exacerbated the clozapine-induced disruption of pup retrieval and nest building. These findings suggest a double dissociation mechanism underlying the disruption of haloperidol and clozapine on rat maternal behavior. Specifically, haloperidol disrupts maternal behavior primarily by blocking dopamine D2 receptors, whereas clozapine exerts its disruptive effect primarily by blocking the 5-HT2A/2C receptors. Our findings also suggest that 5-HT receptors are involved in the mediation of rat maternal behavior.
KW - 5-HT receptor
KW - Clozapine
KW - DOI
KW - Dopamine D/D receptor
KW - Haloperidol
KW - Quinpirole
KW - Rat maternal behavior
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U2 - 10.1016/j.pbb.2009.06.005
DO - 10.1016/j.pbb.2009.06.005
M3 - Article
C2 - 19539643
AN - SCOPUS:67849133187
SN - 0091-3057
VL - 93
SP - 433
EP - 442
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 4
ER -