Carbamazepine Suppresses Methamphetamine-Induced Fos Expression in a Regionally Specific Manner in the Rat Brain Possible Neural Substrates Responsible for Antimanic Effects of Mood Stabilizers

Abstract

Carbamazepine (CBZ) has been widely used for treatment of manic states. Because amphetamine produces effects in humans similar to those of idiopathic mania, acute methamphetamine administration could serve as a model of this condition. To elucidate the neurobiological substrates responsible for the antimanic effects of carbamazepine, this study investigated the effects of chronic carbamazepine administration on regional Fos protein expression induced by a single dose of methamphetamine (2mg/kg). Chronic treatment with CBZ (0.25% in Carbamazepine is a widely used tricyclic anticonvulsant drug. It shares a common clinical profile with lithium for its acute and prophylactic therapeutic effects in bipolar affective disorder (Emilien et al. 1996;Post and Ballenger 1990). Although a wide variety of biochemical and neurophysiological effects (including stabilizing the sodium and potassium channel, reducing calcium fluxes, antagonizing peripheral-type benzodiazepine receptors, up-regulating GABA B receptors, and acting as an adenosine antagonist or agonist) have been described for this drug, the precise mechanism of its mood-stabilizing effects remains unknown (Post et al. 1994). Moreover, the neuroanatomic substrates responsible for the antimanic effects of carbamazepine have not yet been identified.Because such psychostimulants as d-amphetamine and cocaine produce effects in humans that are very similar to the symptoms of idiopathic mania de Wit 1996, 1997;Smith and Davis 1977), it has been proposed that administration of these agents may serve as a model of this condition (Robbins and SaFrom the Department of Neuropsychiatry (YL, TH, KO, MM, SK), Okayama University Medical School, Okayama, Japan; and Takaoka Hospital (YF), Himeji, Japan.Address correspondence to: Dr. T. Hamamura, Department of Neuropsychiatry, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama, 700-8558 Japan.Received June 28, 1999; revised October 26, 1999; accepted November 1, 1999. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 22 , NO . 5 Carbamazepine Suppresses MAP-Induced Fos 531 hakian 1980). Quantification of changes in the expression of the immediate early gene c-fos has proved to be a very useful method of mapping the distribution of neurons that are activated by physiological or pharmacological stimuli (Dragunow and Faull 1989;Morgan and Curran 1991;Sagar et al. 1988). In our previous study (Lee et al. 1999), we investigated the neurobiological substrates involved in the antimanic effects of lithium in a methamphetamine-manic model using Fos mapping. Chronic lithium administration significantly reduced the number of Fos-like immunoreactivity (Fos-LI)-positive nuclei induced by methamphetamine administration in the prefrontal cortex, the nucleus accumbens, the caudate/putamen, and the amygdala.In the previous study, it was hypothesized that these regions were possible neural targets for the antimanic efficacy of lithium. The next step was to identify the specific antimanic target region. The objective of the present study was to...

Tetraspan Protein CD151 A Common Target of Mood Stabilizing Drugs?

“…The low plasma carbamazepine concentrations were comparable to the values obtained by other investigators using a similar dosing regimen (Marangos et al 1985;Lee et al 2000). These low levels are likely a result of differences between the rat and human in the metabolism of these drugs.…”

“…It is unlikely that the reduction in CD151 expression is attributable to the weight loss commonly observed in rats during chronic administration of these mood stabilizers (Baptista et al 1995;Lee et al 2000), as there were no significant differences in weight gain between control and drug-treated animals during the treatment period (Hua et al 2000). Among possible mechanisms that might account for the reduced CD151 expression, altered RNA metabolism through various nuclear events, including rate of transcription, mRNA export, or mRNA degradation, merit further consideration.…”

“…Among possible mechanisms that might account for the reduced CD151 expression, altered RNA metabolism through various nuclear events, including rate of transcription, mRNA export, or mRNA degradation, merit further consideration. In this regard, several lines of evidence indicate that these mood stabilizers modulate c-fos mRNA levels (Miller and Mathe, 1997;Lee et al 2000), and DNA binding activity and/or protein levels of various transcription factors, such as CREB and AP-1 (Ozaki and Chuang 1997;Asghari et al 1998;Yuan et al 1998). These could potentially be involved in the regulation of CD151 expression.…”

In Vivo Evidence in the Brain for Lithium Inhibition of Glycogen Synthase Kinase-3

“…Valproate doses were arrived at within our group by testing various doses. The carbamazepine dose has been used successfully by other groups (Lee et al, 2000;. Owing to the differences in metabolism between rats and humans, the ratios of carbamazepine and carbamazepine 10,11 epoxide (a primary carbamazepine metabolite) are reversed between the species (Marangos et al, 1985).…”

Mood stabilizer psychopharmacology

“…Reports have also found that carbamazepine regulates other additional cellular events that may be related to the drug's mood stabilizers efficacy. For example, carbamazepine attenuates stimulated AP-1 DNA binding [243], reduces CD 151 mRNA levels [244], and suppresses stimulated C-fos levels [62,[245][246][247].…”