Differential changes in glutamatergic transmission via N-methyl-D-aspartate receptors in the hippocampus and striatum of rats behaviourally sensitized to methamphetamine

Abstract

We searched for changes in glutamatergic transmission via N-methyl-D-aspartate (NMDA) receptors in the hippocampus and striatum of rats behaviourally sensitized to methamphetamine (Meth). Prior to being given a challenge dose of Meth (2 mg/kg, s.c.), the rats were given Meth (4 mg/kg, s.c.) five times a week for 3 wk. Seven days after the challenge test, we examined glutamate (Glu) release from hippocampal and striatal slices evoked by 30 mm KCl, and NMDA-evoked dopamine (DA) release from striatal slices. We further immunoquantified NMDAR1, R2A and R2B receptors as well as the fodrin alpha-subunit, a 240 kDa cytoskeletal protein that is cleaved to form 150 kDa limited proteolytic fragments by NMDA receptor stimulation. In the study of KCl-evoked Glu release, Glu release from the hippocampus was 31% lower in the Meth-sensitized rats than in the control rats, while Glu release from the striatum was 34% higher in the Meth-sensitized rats. NMDAR1, R2A and R2B immunoreactivities in the striatum were significantly lower in the Meth-sensitized rats (by 12, 13 and 12%, respectively) than those in the control rats. However, no differences in the immunoreactivities were found for the hippocampus. Immunoquantification of the fodrin alpha-subunit in the hippocampus revealed that 150 kDa fragments were significantly lower (by 10%) in the Meth-sensitized rats than in the control rats. In contrast to the control rats, NMDA-evoked DA release from the striatum was diminished in the Meth-sensitized rats. These results indicate that the activity of the Glu system is functionally decreased in the hippocampus of Meth-sensitized rats, whereas the Glu system in the striatum of Meth- sensitized rats shows adaptive and functional changes in the receptors in response to the increased Glu release.

Neurotoxic Effects of Methamphetamine on Rat Hippocampus Pyramidal Neurons

“…Yamamoto et al (1999) reported that glutamate release from the hippocampus was reduced in the MAP-sensitized rats as compared to control rats, while glutamate release from the striatum was higher in the MAP-sensitized rats. In our experiments, the ratio of amplitude of the presynaptic potential to the population EPSP indicates that MAP decreased glutamate release from the nerve terminal of the Shaeffer collateral, which is consistent with the biochemical observations of Yamamoto et al (1999).…”

“…When damage is sufficient to cause cell death, it is by apoptosis (Deng et al 2002;Zhu et al 2006), likely secondary to generation of reactive oxygen species leading to caspase activation (Pubill et al 2005;Jiménez et al 2004;Yamamoto and Bankson 2005). Yamamoto et al (1999) reported that glutamate release from the hippocampus was reduced in the MAP-sensitized rats as compared to control rats, while glutamate release from the striatum was higher in the MAP-sensitized rats. In our experiments, the ratio of amplitude of the presynaptic potential to the population EPSP indicates that MAP decreased glutamate release from the nerve terminal of the Shaeffer collateral, which is consistent with the biochemical observations of Yamamoto et al (1999).…”

Lamotrigine blocks repeated high-dose methamphetamine-induced behavioral sensitization to dizocilpine (MK-801), but not methamphetamine in rats

“…Repeated administration of METH reduces the protein levels of NMDA receptors, including NMDA receptor 1 (NR1), in the hippocampus [22]. In addition, repeated administration of METH reduces immunoreactivities of NR1 and NMDA receptors comprising NMDA receptor 2A and 2B in the striatum [26]. Continuous stimulation of NMDA receptors induces desensitization of this type of receptor [13,14].…”

Valproate blocks high-dose methamphetamine-induced behavioral cross-sensitization to locomotion-inducing effect of dizocilpine (MK-801), but not methamphetamine

“…Repeated administration of METH (4 mg/kg) reduces NMDAR1, R2A, and R2B immunoreactivity in the striatum (Yamamoto et al 1999). Similarly, repeated AMPH administration induces longlasting down-regulation of NMDAR1 mRNA and protein levels in the NAC and prefrontal cortex (PFC) (Lu et al 1999).…”