The effect of lithium on methamphetamine-induced regional Fos protein expression in the rat brain

Abstract

Lithium has been used widely for the treatment of manic states. Since amphetamines produce effects in humans similar to the symptoms of idiopathic mania, amphetamine administration to animals has been proposed as a model of this condition. To investigate the neurobiologic substrates of the antimanic effects of chronic lithium administration, we investigated its effects on methamphetamine-induced regional Fos protein expression in the rat brain. Chronic lithium administration (14 days; serum lithium concentration, 0.41+/-0.02 mEq/l) significantly reduced the number of neuronal nuclei showing immunoreactivity induced by methamphetamine (2mg/kg) in the prefrontal cortex, caudate/putamen, nucleus accumbens, and central nucleus of the amygdala. These results indicate the structural basis in CNS which is responsible for the antimanic effect of lithium.

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

“…In contrast, our previous study (Lee et al 1999) showed that lithium treatment significantly reduced the number of these neurons in the prefrontal cortex and the central amygdaloid nucleus, as well as in the nucleus accumbens and the caudate/putamen. Thus, the core of the nucleus accumbens and the caudate/putamen are common target regions in which both CBZ and lithium treatments suppress methamphetamine-induced Fos expression.…”

“…Thus, the core of the nucleus accumbens and the caudate/putamen are common target regions in which both CBZ and lithium treatments suppress methamphetamine-induced Fos expression. In these regions, chronic lithium administration significantly attenuates the number of methamphetamine-induced Fos-LI-positive neurons by approximately 40-65% (Lee et al 1999), and chronic CBZ administration significantly attenuates it by approximately 32-39% (Table 1). The caudate/putamen (especially the medial section) and the nucleus accumbens are closely related to emotion and serve as output organs of reward to the motor system (Fibiger and Phillips 1986;Mogenson et al 1980;Robbins and Everitt 1996).…”

“…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.…”

Functional Internal Complexity of Amygdala: Focus on Gene Activity Mapping After Behavioral Training and Drugs of Abuse

“…Acute methamphetamine injection has been shown to induce c-Fos protein expression in the central and medial (480) or in the central and basolateral nuclei (265,266). In all these studies, other amygdalar nuclei were not analyzed.…”

Methamphetamine: A molecular and pathological exacerbate of HIV neurocognitive disorder

“…For example, the acute administration of MA to rodents resulted in production of oxidative stress as demonstrated by reduced glutathione and increased oxidized glutathione levels in the rat striatum and prefrontal cortex (Acikgoz et al 1998, Harold et al 2000. MA induced oxidative stress in mice has also been observed to activate redox-responsive transcription factors such as activator protein-1 (AP-1) and cAMPresponsive element binding protein (CREB) (Lee et al 1999).…”