Prenatal Bupropion Exposure Enhances the Cocaine Reward and Stress SuscEptibility in Adult Mice

S-Y. Hsiao；C-F. G. Cherng；Y-K. Yang；T-L. Yeh；L. Yu

SSRI ； NDRI ； SARI ； psychomotor stimulant ； CPP ； anxiety

The Chinese Journal of Physiology

48卷4期（2005 / 12 / 31）

223 - 229

英文

Although a growing body of evidence supports the notion that certain antidepressant treatments in pregnancy produce earlier delivery and minor behavioral teratogenesis in infants, the long-term effects of such treatments in adulthood remain ill-defined. Recently, postnatal exposure to psychotropic drugs was found to affect the emotional development and susceptibility to abused drugs. Thus, this study aimed to examine whether prenatal exposure of four frequently-used antidepressants, bupropion, fluvoxamine, citalopram, and trazodone, altered the responsiveness to stress and cocaine in the adulthood. Dams received daily injection of bupropion (25 or 12.5 mg/kg), citalopram (5 mg/kg), fluvoxamine (10 mg/kg), trazodone (20 mg/kg) or saline throughout their third trimester of gestation, and several birth outcome indices were then examined. Locomotor activity, naive anxiety levels, and the sensitivity to the cocaine reinforcing effects ere observed in pups at their day 56-60 post partum. We found that trazodone treatment produced a high mortality rate in pups after weaning. Mice, prenatally treated with bupropion at 25 mg/kg, exhibited lower rearing numbers and ambulatory activity as compared to the saline-treated mice. More importantly, such treatment enhanced the mouse sensitivity to the reinforcing effects of cocaine. Taken together, these results suggest that use of bupropion in the late pregnancy may run a risk of enhancing the offspring's susceptibility to stress and cocaine reward in adulthood.

1. Lien, W.H.,Yeh, T.L.,Yang, Y.K.,Cherng, C.F.,Chen, H.H.,Chen, P.S.,Yu, L.(2004).Cycloheximide enhances maintenance of methamphetamine-induced conditioned place preference.Chinese J. Physiol,47,23-30.
   連結：
2. Andersen, S.L.,Arvanitogiannis, A.,Pliakas, A.M.,LeBlanc, C.,Carlezon, W.A.(2001).Altered responsiveness to cocaine in rats exposed to methylphenidate during development.Nat. Neurosci,5,13-14.
3. Ansorge, M.S.,Zhou, M.,Lira, A.,Hen, R.,Gingrich, J.A.(2004).Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice.Science,306,879-881.
4. Bals-Kubic, R.,Ableitner, A.,Herz, A.,Shippenberg, T. S.(1993).Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats.J. Pharmacol. Exp. Ther.,264,489-495.
5. Chambers, C.D.,Johnson, K.A.,Dick, L.M.,Felix, R.J.,Jones, K.L.(1996).Birth outcomes in pregnant women taking fluoxetine.NEJM,335,1010-1015.
6. Christensen, H.D.,Rayburn, W.F.,Gonzalez, C.L.(2000).Chronic prenatal exposure to paroxetine (Paxil) and cognitive development of mice offspring.Neurotoxic. Teran,22,733-739.
7. Cohen, L.S.,Heller, V.L.,Bailey, J.W.,Grush, L.,Ablon, J.S.,Bouffard, S.M.(2000).Birth outcomes following prenatal exposure to fluoxetine.Biol. Psychiat,48,996-1000.
8. Cohen, L.S.,Rosenbaum, J.F.(1998).Psychotropic drug use during pregnancy: weighing the risks.J. Clin. Psychia,59(s.2),18-28.
9. Coleman, F.H.,Christensen, H.D.,Gonzalez, C.L.,Rayburn, W.F.(1999).Behavioral changes in developing mice after prenatal exposure to paroxetine (Paxil).Am. J. Obste. Gynecol,181,1166-1171.
10. DaSilva, V.A.,Altenburg, S.P.,Malherios, L.R.,Thomaz, T.G.,Lindsey, C.J.(1999).Postnatal development of rats exposed to fluvoxemine or venlafaxine during the third week of pregnancy.Braz. J. Med. Biol. Res.,32,93-98.
11. Di Matteo, V.,Di Giovanni, G.,Di Mascio, M.,Esposito, E.(1998).Selective blockade of serotonin2C/2B receptors enhances dopamine release in the rat nucleus accumbens.Neuropharmcology,37,265-272.
12. Faron-Gorecka, A.,Kusmider, M.,Inan, S.Y.,Siwanowicz, J.,Dziedzicka-Wasylewska, M.(2004).Effects of tramadol on alpha2-adrenergic receptors in the rat brain.Brain Res.,1016,263-267.
13. Feighner, J.P.(1999).Mechanism of action of antidepressant medications.J. Clin. Psychia,60(suppl 4),4-11.
14. Goldstein, D.J.(1995).Effects of third trimester fluoxetine exposure on the newborn.J. Clin. Psychopharm,14,417-420.
15. Gotlib, I.H.,Whiffen, V.E.,Mount, J.H.(1989).Prevalence rates demographic characteristics associated with depression in pregnancy and postpartum.J. Consult. Clin. Psychol,57,269-274.
16. Gregory, E.S.,Michael, L.C.,Robert, L.D.(2002).Outcomes of prenatal antidepressant exposure.Am. J. Psychia,159,2055-2061.
17. Hachisu, M.,Ichimaru, Y.(2000).Pharmacological and clinical aspects of fluvoxamine (Depromel), the first selective serotonin reuptake inhibitor approved for clinical use employed in Japan.Nippon Yakurigaku Zasshi-Folia Pharmacologica Japonica,115,271-279.
18. Hendrick, V.,Stowe, Z. N.,Altshuler, L. L.,Hwang, S.,Lee, E.,Haynes, D.(2003).Placental passage of antidepressant medications.Am. J. Psychia,160,993-996.
19. Herges, S.,Taylor, D.A.(2000).Involvement of 5-HT(3) receptors in the nucleus accumbens in the potentiation of cocaine-induced behaviors in the rat.Brit. J. Pharm,131,1294-1302.
20. Holcomb, W.L.,Stone, L.S.,Lustman, P.J.,Gavard, J.A.,Mostello, D.J.(1996).Screening for depression in pregnancy: characteristics of the Beck depression inventory.Intern. J. Gynecol. Obste,88,1021-1025.
21. Horst, W.D.,Preskorn, S.H.(1998).Mechanisms of action and clinical characteristics of three atypical antidepressants: venlafaxine, nefazodone, bupropion.J. Affect. Disor.,51,237-254.
22. Kulin, N.A.,Pastuszak, A.,Sage, S.R.,Schick-Boschetto, B.,Spivey, G.,Feldkamp, M.,Ormond, K.,Matsui, D.,Stein- Schechman, A.K.,Cook, L.,Brochu, J.,Rieder, M.,Koren, G.(1998).Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors: a prospective control multicenter study.JAMA,279,609-610.
23. Marcoli, M.,Maura, G.,Tortarolo, M.,Raiteri, M.(1998).Trazodone is a potent agonist at 5-HT2c receptor mediating inhibition of the NMethyl-D-Aspartate/Nitric Oxide/Cyclic GMP pathway in rat cerebellum.J. Pharm. Exper. Ther.,285,983-986.
24. Marcus, S.M.,Barry, K.L.,Glynn, H.A.,Tandon, R.,Greden, J.F.(2001).Treatment guidelines for depression in pregnancy.Intern. J. Gynecol. Obste.,72,61-70.
25. Marek, G.J.,Mcdougle, C.J.,Price, L.H.,Seiden, L.S.(1992).A comparison of trazodone and fluoxetine: implications for a serotonergic mechanism of antidepressant action.Psychopharmcology,109,2-11.
26. McMahon, L.R.,Cunningham, K.A.(1999).Antagonism of 5-hydrox hydroxytryptamine(4) receptors attenuates hyperactivity induced by cocaine: putative role for 5-hydroxytryptamine(4) receptors in the nucleus accumbens shell.J. Pharm. Exp. Ther.,291,300-307.
27. Muller, C.P.,Thonnessen, H.,Jocham, G.,Barros, M.,Tomaz, C.,Carey, R.J.,Huston, J.P.(2004).Cocaine-induced `active immobility` and its modulation by the serotonin1A receptor.Behav. Pharmacol,15,481-493.
28. Nulman, I.,Bovet, J.,Stewart, D.E.,Wolpin, J.,Gardner, H.A.,Theis, J.G..W.,Kulin, N.,Koren, G.(1997).Neurodevelopment of children exposed in utero to antidepressant drugs.NEJM,336,258-262.
29. Pohland, R.C.,Byrd, T.K.,Hamilton, M.,Koons, J.R.(1989).Placental transfer and fetal distribution of fluoxetine in the rat.Toxicol. Appl. Pharmacol,98,198-205.
30. Preskorn, S.H.,Othmer, S.C.(1984).Evaluation of bupropion hydrochloride: the first of a new class of atypical antidepressants.Psychopharmcology,4,20-34.
31. Sasaki-Adams, D.M.,Kelley, A.E.(2001).Serotonin-dopamine interactions in the control of conditioned reinforcement and motor behavior.Neuropsychopharmcology,25,440-452.
32. Singh, Y.,Jaiswal, A.K.,Bhattacharya, S.K.(1998).Effect of prenatal diazepam, phenobarbital, haloperidol and fluoxetine exposure on foot shock induced aggression in rats.Ind. J. Exper. Biol,36,1023-1024.
33. Stephen, M. S.(1998).Selecting an antidepressant by using mechanism of action to enhance efficacy and avoid side effects.J. Clin. Psychia,59(s.18),23-29.
34. Stone, E.A.,Lin, Y.,Ahsan, R.,Quartermain, D.(2004).Gross mapping of alpha1-adrenoceptors that regulate behavioral activation in the mouse brain.Behav. Brain Res.,152,167-175.
35. Tuinstra, T.,Cobelens, P.,Lubbers, L.,Verheij, M.,Cools, A.R.(2002).High and low responders to novelty and mesolimbic norepinephrine: effects of noradrenergic agents on radial-maze performance.Behav. Neurosci,116,1084-1092.
36. Tuinstra, T.,Cools, A.R.(2000).Newly synthesized dopamine in the nucleus accumbens is regulated by beta-adrenergic, but not alphaadrenergic, receptors.Neuroscience,98,743-747.
37. Vorhee, C.V.,Acuff-Smith, K.D.,Schiling, M.A.,Fisher, J.E.,Moran, M.S.,Buelke-Sam, J.A.(1994).Developmental neurotoxicity evaluation of the effects of prenatal exposure to fluoxetine in rats.Funda. Appl. Toxicol,23,194-205.

1. Yu, Lung,Su, Shu-Wen,Lin, Yin Chiu,Cherng, Chian-Fang G.(2007).Prenatal Exposure of Bupropion May Enhance Agitation, Anxiety Responses, and Sensitivity to Cocaine Effects in Adult Mice.Chinese Journal of Physiology,50(1),1-8.