Effects of Novel Antipsychotics, Amisulpiride and Aripiprazole, on Maternal Behavior in Rats

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2005 Jul 19

PMID 16025315

Citations 12

Authors

Ming Li

Radek Budin

Alison S Fleming

Shitij Kapur

Affiliations

Soon will be listed here.

Abstract

Rationale: Rat maternal behavior, which entails complex motivational and social factors, is disrupted by the currently available typical and atypical antipsychotics. It is thought that this disruption reflects a side effect of antipsychotics, modeling the neuroleptic-induced negative or deficit state. Amisulpiride and aripiprazole are new atypical antipsychotics with mechanisms of action distinct from the current typical and atypical antipsychotics. The effects of these drugs on maternal behavior have not been explored.

Objective: In the present study, we systematically examined the behavioral effects of amisulpiride and aripiprazole on maternal behavior in postpartum female rats.

Methods: Various components of maternal behavior (pup retrieval, pup licking, nest building and pup nursing) were examined repeatedly over a period of 24 h after a single injection of three doses of amisulpiride (10, 30, and 100 mg/kg s.c.) and aripiprazole (3, 10, and 30 mg/kg).

Results: Amisulpiride at the lower doses (10 and 30 mg/kg) enhanced pup licking, and only at the highest dose disrupted the active components of maternal behavior such as pup retrieval and nest building. Its effect was delayed in onset and prolonged as compared to other antipsychotics. Aripiprazole, even at the highest dose (30 mg/kg) did not impair pup retrieval or pup licking. However, it did disrupt nest building and led to enhanced pup nursing.

Conclusions: The unique effects of these two drugs may be due to their unique actions at the mesolimbic dopamine synapses. The sparing of the major components of maternal behavior by aripiprazole may be related to its partial agonist effects, whereas the enhancement of pup licking by amisulpiride may be related to its dose-dependent preferential effect on the presynaptic autoreceptors. The potential clinical implications of these findings are discussed.

Citing Articles

Antipsychotic drugs on maternal behavior in rats.

Li M Behav Pharmacol. 2015; 26(6):616-26.

PMID: 26221833 PMC: 4520249. DOI: 10.1097/FBP.0000000000000168.

Repeated administration of aripiprazole produces a sensitization effect in the suppression of avoidance responding and phencyclidine-induced hyperlocomotion and increases D2 receptor-mediated behavioral function.

Gao J, Qin R, Li M J Psychopharmacol. 2015; 29(4):390-400.

PMID: 25586399 PMC: 4757439. DOI: 10.1177/0269881114565937.

Effects of 5-hydroxytryptamine 2C receptor agonist MK212 and 2A receptor antagonist MDL100907 on maternal behavior in postpartum female rats.

Chen W, Zhang Q, Su W, Zhang H, Yang Y, Qiao J Pharmacol Biochem Behav. 2013; 117:25-33.

PMID: 24321440 PMC: 4034582. DOI: 10.1016/j.pbb.2013.11.034.

Repeated aripiprazole treatment causes dopamine D2 receptor up-regulation and dopamine supersensitivity in young rats.

Varela F, Der-Ghazarian T, Lee R, Charntikov S, Crawford C, McDougall S J Psychopharmacol. 2013; 28(4):376-86.

PMID: 24045880 PMC: 5673084. DOI: 10.1177/0269881113504016.

Maternal behavior in basic science: translational research and clinical applicability.

Pires G, Tufik S, Giovenardi M, Andersen M Einstein (Sao Paulo). 2013; 11(2):256-60.

PMID: 23843071 PMC: 4872904. DOI: 10.1590/s1679-45082013000200021.

References

Silva M, Bernardi M, Felicio L . Effects of dopamine receptor antagonists on ongoing maternal behavior in rats. Pharmacol Biochem Behav. 2001; 68(3):461-8. DOI: 10.1016/s0091-3057(01)00471-3. View

Stern J, Taylor L . Haloperidol inhibits maternal retrieval and licking, but enhances nursing behavior and litter weight gains in lactating rats. J Neuroendocrinol. 2009; 3(6):591-6. DOI: 10.1111/j.1365-2826.1991.tb00323.x. View

Delcker A, Schoon M, Oczkowski B, Gaertner H . Amisulpride versus haloperidol in treatment of schizophrenic patients--results of a double-blind study. Pharmacopsychiatry. 1990; 23(3):125-30. DOI: 10.1055/s-2007-1014494. View

Hansen S, Harthon C, Wallin E, Lofberg L, Svensson K . Mesotelencephalic dopamine system and reproductive behavior in the female rat: effects of ventral tegmental 6-hydroxydopamine lesions on maternal and sexual responsiveness. Behav Neurosci. 1991; 105(4):588-98. DOI: 10.1037//0735-7044.105.4.588. View

Stern J, Keer S . Maternal motivation of lactating rats is disrupted by low dosages of haloperidol. Behav Brain Res. 1999; 99(2):231-9. DOI: 10.1016/s0166-4328(98)00108-9. View

Nakai S, Hirose T, Uwahodo Y, Imaoka T, Okazaki H, Miwa T . Diminished catalepsy and dopamine metabolism distinguish aripiprazole from haloperidol or risperidone. Eur J Pharmacol. 2003; 472(1-2):89-97. DOI: 10.1016/s0014-2999(03)01857-0. View

Perrault G, Depoortere R, Morel E, Sanger D, Scatton B . Psychopharmacological profile of amisulpride: an antipsychotic drug with presynaptic D2/D3 dopamine receptor antagonist activity and limbic selectivity. J Pharmacol Exp Ther. 1997; 280(1):73-82. View

Hansen S, Stanfield E, Everitt B . The effects of lesions of lateral tegmental noradrenergic neurons on components of sexual behavior and pseudopregnancy in female rats. Neuroscience. 1981; 6(6):1105-17. DOI: 10.1016/0306-4522(81)90075-0. View

Li M, Fleming A . Differential involvement of nucleus accumbens shell and core subregions in maternal memory in postpartum female rats. Behav Neurosci. 2003; 117(3):426-45. DOI: 10.1037/0735-7044.117.3.426. View

10.

Hummer M, Kemmler G, Kurz M, Kurzthaler I, Oberbauer H, Fleischhacker W . Sexual disturbances during clozapine and haloperidol treatment for schizophrenia. Am J Psychiatry. 1999; 156(4):631-3. DOI: 10.1176/ajp.156.4.631. View

11.

Goudie A, Taylor A . Comparative characterisation of the discriminative stimulus properties of clozapine and other antipsychotics in rats. Psychopharmacology (Berl). 1998; 135(4):392-400. DOI: 10.1007/s002130050527. View

12.

Riordan D, Appleby L, Faragher B . Mother-infant interaction in post-partum women with schizophrenia and affective disorders. Psychol Med. 1999; 29(4):991-5. DOI: 10.1017/s0033291798007727. View

13.

Shapiro D, Renock S, Arrington E, Chiodo L, Liu L, Sibley D . Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology. 2003; 28(8):1400-11. DOI: 10.1038/sj.npp.1300203. View

14.

Rowland D, Steele M, Moltz H . Serotonergic mediation of the suckling-induced release of prolactin in the lactating rat. Neuroendocrinology. 1978; 26(1):8-14. DOI: 10.1159/000122765. View

15.

Kikuchi T, Tottori K, Uwahodo Y, Hirose T, Miwa T, Oshiro Y . 7-(4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2(1H)-quinolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity. J Pharmacol Exp Ther. 1995; 274(1):329-36. View

16.

Wadenberg M, Kapur S, Soliman A, Jones C, Vaccarino F . Dopamine D2 receptor occupancy predicts catalepsy and the suppression of conditioned avoidance response behavior in rats. Psychopharmacology (Berl). 2000; 150(4):422-9. DOI: 10.1007/s002130000466. View

17.

Natesan S, Reckless G, Nobrega J, Fletcher P, Kapur S . Dissociation between in vivo occupancy and functional antagonism of dopamine D2 receptors: comparing aripiprazole to other antipsychotics in animal models. Neuropsychopharmacology. 2005; 31(9):1854-63. DOI: 10.1038/sj.npp.1300983. View

18.

Naber D, Lambert M . Aripiprazole: a new atypical antipsychotic with a different pharmacological mechanism. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28(8):1213-9. DOI: 10.1016/j.pnpbp.2004.06.020. View

19.

Protais P, HERMIER C, Costentin J . The discriminant dopamine antagonist property of benzamides is observed at various times after their systemic or intracerebroventricular administration. Neuropharmacology. 1985; 24(9):861-7. DOI: 10.1016/0028-3908(85)90037-1. View

20.

Giordano A, Johnson A, Rosenblatt J . Haloperidol-induced disruption of retrieval behavior and reversal with apomorphine in lactating rats. Physiol Behav. 1990; 48(1):211-4. DOI: 10.1016/0031-9384(90)90288-f. View