Abstract
There is much speculation regarding the effects of estrogen withdrawal at the end of pregnancy on forebrain dopamine, however, few studies have directly examine changes in this system postpartum. The present work sought to determine what changes in forebrain dopamine function occur in the postpartum rat. Specifically, prepulse inhibition of the acoustic startle response (PPI) was measured in primiparous female rats on postpartum day 2 (PPD2) or 14 (PPD14) following treatment with saline or the dopamine D2 agonist, quinpirole. Diestrus (DI) females served as controls. Dopamine content and turnover as well as cyclic AMP (cAMP) accumulation were determined within the nucleus accumbens and dorsal striatum in these same females. In addition, circulating levels of plasma corticosterone, estradiol and progesterone were measured. PPI was significantly disrupted in both postpartum groups. This effect was associated with decreased cAMP content within the nucleus accumbens. Quinpirole treatment (0.1 and 0.5 mg/kg) dose-dependently disrupted PPI in DI controls while PPD2 and PPD14 animals demonstrated reduced sensitivity to the D2 agonist. PPD14 animals demonstrated increased startle amplitude, an effect that was attenuated by quinpirole treatment. PPD14 females were also less sensitive to quinpirole-mediated reductions in DA turnover within the nucleus accumbens and both PPD2 and PPD14 females had an attenuated response to the stimulatory effects of quinpirole on corticosterone secretion. Collectively these findings suggest that the postpartum period is associated with reduced sensorimotor gating and altered forebrain DA systems, which may be related to shifts in circulating hormones.
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References
Ahokas A, Aito M (1999). Role of estradiol in puerperal psychosis. Psychopharmacology 147: 108–110.
Ahokas A, Aito M, Rimon R (2000). Positive treatment effect of estradiol in postpartum psychosis: a pilot study. Journal of Clinical Psychiatry 61: 166–169.
Borowsky B, Kuhn CM (1992). D1 and D2 dopamine receptors stimulate hypothalao-pituitary-adrenal activity in rats. Neuropharmacology 31: 671–678.
Braff DL, Geyer MA, Swerdlow NR (2001). Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology 156: 234–258.
Byrnes EM, Byrnes JJ, Bridges RS (2001). Increased sensitivity of dopamine systems following reproductive experience in rats. Pharmacol Biochem Behav 68: 481–489.
Culm KE, Lim AM, Onton JA, Hammer RP (2003). Reduced Gi and Go protein function in the rat nucleus accumbens attenuates sensorimotor gating deficits. Brain Res 982: 12–18.
Foreman MM, Fuller RW, Hynes MD, Gidda JS, Nichols CL, Schaus JM et al (1989). Preclinical studies on quinelorane, a potent and highly selective D2-dopaminergic agonist. J Pharmacol Exp Therapeut 250: 227–235.
Fuller RW, Snoddy HD, Mason NR, Clemens JA, Bemis KG (1983). Elevation of serum corticosterone in rats by dopamine agonists related in structure to pergolide. Neuroendocrinology 36: 285–290.
Huber TJ, Rollnik J, Wilhelms J, von zur Muhlen A, Emrich HM, Schneider U (2001). Estradiol levels in psychotic disorders. Psychoneuroendocrinol 26: 27–35.
Ikemoto S, Goeders NE (1998). Microinjections of dopamine agonists and cocaine elevate plasma corticosterone: dissociation effects among the ventral and dorsal striatum and medial prefrontal cortex. Brain Res 814: 171–178.
Jovanovic T, Szilagyi S, Chakravorty S, Fiallos AM, Lewison BJ, Parwani A et al (2004). Menstrual cycle phase effects on prepulse inhibition of acoustic startle. Psychophysiology 41: 401–406.
Kaplan GB, Sethi RK, McClelland EG, Leite KA (1998). Regulation of G protein-mediated adenylyl cyclase in striatum and cortex of opiate-dependent and opiate withdrawing mice. Brain Res 788: 104–110.
Koch M (1998). Sensorimotor gating changes across the estrous cycle in female rats. Physiol Behav 64: 625–628.
Kohl C (2004). Postpartum psychoses: closer to schizophrenia or the affective spectrum? Curr Opin Psychiatry 17: 87–90.
Lightman SL, Young WS (1989). Lactation inhibits stress-mediated secretion of corticosterone and oxytocin and hypothalamic accumulation of corticotrophin-releasing factor and enkephalin messenger ribonucleic acids. Endocrinology 124: 2358–2364.
Meakin CJ, Brockinton IF, Lynch SE, Jones SR (1995). Dopamine supersensitivity and hormonal status in puerperal psychosis. Br J Psychiatry 166: 73–79.
Munirathiam G, Yoburn BC (1994). A simple procedure for assaying cAMP. Pharmacol Biochem Behav 48: 813–816.
Paxinos G, Watson C (1998). The Rat Brain in Stereotaxic Coordinates. Academic Press: New York.
Putnam CD, Brann DW, Mahesh VB (1991). Acute activation of the adrenocorticotropin-adrenal axis: effect on gonadotropin and prolactin secretion in the female rat. Endocrinology 128: 2558–2566.
Rupprecht R, Koch M, Montkowski A, Lancel M, Faulhaber J, Harting J et al (1999). Assessment of neuroleptic-like properties of progesterone. Psychophamacology 143: 29–38.
Seyfried LS, Marcus SM (2003). Postpartum mood disorders. Int Rev Psychiatry 15: 231–242.
Swerdlow NR, Braff DL, Masten VL, Geyer MA (1990). Schizophrenia-like sensorimotor gating abnormalities in rats following dopamine infusion into the nucleus accumbens. Psychopharmacology 101: 414–420.
Swerdlow NR, Hartman PL, Auerbach PP (1997). Changes in sensorimotor inhibition across the menstrual cycle: implications for neuropsychiatric disorders. Biol Psychiatry 41: 452–460.
Swerdlow NR, Martizez ZA, Hanlon FM, Platten A, Farid M, Auerbach P et al (2000). Toward understanding the biology of a complex phenotype: Rat strain and substrain differences in the sensorimotor gating-disruptive effects of dopamine agonists. J Neurosci 20: 4325–4336.
Toufexis DJ, Rochford J, Walker CD (1999). Lactation-induced reduction in rats' acoustic startle is associated with changes in noradrenergic neurotransmission. Behav Neurosci 113: 176–184.
Van den Buuse M, Eikelis N (2001). Estrogen increases prepulse inhibition of acoustic startle in rats. Eur J Pharmacol 425: 33–41.
Wan FJ, Geyer MA, Swerdlow NR (1994). Accumbens D2 modulation of sensorimotor gating in rats: assessing anatomical localization. Pharmacol Biochem Behav 49: 115–163.
Wan FJ, Swerdlow NR (1993). Intra-accumbens infusion of quinpirole impairs sensorimotor gating of acoustic startle in rats. Psychopharmacology 113: 103–109.
Woodside B, Abizaid A, Caporale M (1998). The role of specific macronutrient availability in the effect of food restriction on length of lactational diestrus in rats. Physiol Behav 64: 409–414.
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This work was supported in part by Grants R01 HD39895 (RSB) and P30 NS047243 (Dr F Rob Jackson).
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Byrnes, E., Bridges, R., Scanlan, V. et al. Sensorimotor Gating and Dopamine Function in Postpartum Rats. Neuropsychopharmacol 32, 1021–1031 (2007). https://doi.org/10.1038/sj.npp.1301222
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DOI: https://doi.org/10.1038/sj.npp.1301222
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