Methamphetamine-induced neural and cognitive changes in rodents

ArticleinAddiction 102 Suppl 1(s1):61-9 · May 2007with20 Reads
DOI: 10.1111/j.1360-0443.2006.01780.x · Source: PubMed
Abstract
Although psychostimulant drug abuse carries with it several potential health risks, the chronic abuse of amphetamines carries the danger of permanent brain injury. The purpose of these experiments is to develop animal models to understand the long-lasting influences of methamphetamine exposure on cerebral cortex and cognitive function. The approach taken is to administer a regimen of methamphetamine known to be neurotoxic to dopamine and serotonin nerve terminals in the rat, and to investigate the influences of that dosing regimen on (i) cortical neuron integrity and function using anatomical stains and (ii) novel object recognition memory. In rodents, repeated administration of methamphetamine during a single day produces long-lasting damage to striatal dopamine and forebrain serotonin terminals as well as degeneration of somatosensory cortical neurons. The degeneration of somatosensory cortical neurons may represent only the most visible form of long-term deleterious effects on cerebral cortex, as exposure of rats to methamphetamine can reduce the immediate early gene responses of neurons in widespread cortical areas, even long after exposure to the drug. Together with the death and long-lasting functional impairments of cortical neurons, rats exposed to methamphetamine have impaired cognitive function. When tested for object recognition memory, methamphetamine-treated rats show deficiencies lasting for at least 3 weeks after drug exposure. Using a rodent model, these findings provide an avenue to study the cortical influences of methamphetamine and their cognitive sequelae.
    • "These effects predict changes in face sensory processing after extended MA exposure. Indeed, exposure to MA has been previously shown to induce damage to whisker somatosensory cortical neurons, which was associated with increased stereotypical whisker movements [54] and was prevented by the removal of whiskers [55, 56]. In addition, increased BGluM was also observed in the insular cortex and reticular formation . "
    [Show abstract] [Hide abstract] ABSTRACT: Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA-induced neurotoxicity.
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    • "A recent study demonstrated that AMPH mimics the neurochemical profile of aging in rats and impairs memory (Melo et al. 2012). Furthermore, a large number of studies report that AMPHtreated rats show deficiencies in recognition (Schroder et al. 2003; Marshall et al. 2007; Melo et al. 2012) and spatial working (Nagai et al. 2007) memory. It has also been reported that AMPH induces negative states as depression and anxiety (Nesse and Berridge 1997; Cruickshank and Dyer 2009). "
    [Show abstract] [Hide abstract] ABSTRACT: Fenproporex (Fen) is an amphetamine-based anorectic; amphetamine use causes a broad range of severe cognitive deficits and anxiogenic-like effects. In this study we evaluated pharmacological effects of the chronic administration of Fen on cognitive and non-cognitive behaviors. Male adult Wistar rats received intraperitoneal administration of vehicle (control group) or Fen (6.25, 12.5 or 25 mg/kg) for 14 days; the animals were then subjected to habituation and object recognition tasks in open-field apparatus, and elevated plus-maze task. The administration of Fen (12.5 and 25 mg/kg) impaired habituation during the second exposure to the habituation task. In addition, the same doses of Fen also impaired the performance in object recognition task. In elevated plus-maze task, the administration of Fen (in all doses tested) induced anxiogenic-like effects in rats. Our results suggest that chronic Fen administration alters memory and induces anxiogenic-like effects in rats.
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    • "In patients showing such high levels of alpha2 spectral power a reduction was observed after 4 months treatment with rasagiline possibly indicating normalization of dopaminergic transmission. In PD, cognitive disturbances are reported to go hand-in-hand with sleep problems [17] , and preclinical studies in rodents indicate that methamphetamine causes serious neural and cognitive changes lasting for more than 3 weeks [18]. Replacement of selegiline with rasagiline, which is metabolized to aminoindan, was shown in thisFigure 6. Result of discriminant analysis based on all 102 variables (17 electrode positions times 6 frequency ranges). "
    Full-text · Article · Jan 2014
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