Brain regions and monoaminergic neurotransmitters that are involved in mouse ambulatory activity promoted by bupropion

Toyoshi Umezu; Yasuyuki Shibata

doi:10.1016/j.toxrep.2016.06.005

Brain regions and monoaminergic neurotransmitters that are involved in mouse ambulatory activity promoted by bupropion

Toxicol Rep. 2016 Jun 21:3:552-562. doi: 10.1016/j.toxrep.2016.06.005. eCollection 2016.

Authors

Toyoshi Umezu¹, Yasuyuki Shibata¹

Affiliation

¹ Biological Imaging and Analysis Section, Center for Environmental Measurement and Analysis, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.

Abstract

Bupropion (BUP), a substituted phenyl-ethylamine, has been utilized for the treatment of depression and for smoking cessation, however, one concern is that BUP may increase a risk of psychosis similar to other substituted phenyl-ethylamine amphetamine (AMPH) and methamphetamine (MetAMPH). BUP promotes ambulation in mice and causes behavioral sensitization on the ambulation-promoting effect when repeatedly administered as well as AMPH and MetAMPH. The present study aimed to elucidate brain regions and monoaminergic neurotransmitters that are involved in the ambulation-promoting effect of BUP. c-Fos-like immunoreactivity (c-Fos-IR) mapping in brain in combination with measuring ambulatory activity was conducted to determine brain region(s) that is involved in the ambulatory effect of BUP. Three kinds of statistical analyses for c-Fos-IR in 24 brain regions consistently showed that c-Fos-IR in the Caudate putamen (CPu) is positively correlated with the ambulatory response to BUP. In addition, multiple regression analysis indicated that the ambulatory response is a function of c-Fos-IR not only in the CPu but also in the lateral septum nucleus (LS), median raphe nucleus (MnR), lateral globus pallidus (LGP), medial globus pallidus (MGP), locus coeruleus (LC) and ventral hypothalamic nucleus (VMH). Effects of BUP on monoaminergic neurotransmitters in the CPu were examined using in vivo microdialysis method, as the pharmacological experiments indicated that monoaminergic neurotransmitters, dopamine (DA) in particular, mediate the ambulatory response to BUP. Response of DA in the CPu to BUP was parallel to the ambulatory response, showing that DA in the CPu is involved in the ambulatory response to BUP. The present study also suggests that other brain regions such as the LC, the origin nucleus of norepinephrine (NE) neurons, and another neurotransmitter NE may also play some roles for the ambulatory response to BUP, however, further studies are needed to elucidate the roles.

Keywords: Ambulatory activity; Bupropion (PubChem CID: 62884); Chlorpromazine HCl (PubChem CID: 6240); Dopamine; Fluphenazine 2HCl (PubChem CID: 67356); Haloperidol (PubChem CID: 3559); Microdialysis; Mouse; Pimozide (PubChem CID: 16362); Reserpine (PubChem CID: 5770); Spiperone (PubChem CID: 5265); Striatum; c-Fos mapping; α-Methyl-p-tyrosine (PubChem CID: 3125).