Methamphetamine Induces Long-Term Alterations in Reactivity to Environmental Stimuli: Correlation with Dopaminergic and Serotonergic Toxicity

Bortolato, Marco; Frau, Roberto; Piras, Antonio; Luesu, William; Bini, Valentina; Diaz, Giacomo; Gessa, G L; Ennas, Maria Grazia; Castelli, Paola

doi:10.1007/s12640-009-9024-2

Cited by 16 publications

(10 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The validity of our model of METH neurotoxicity is further strengthened by the finding that a METH dose lower than that we used here (4 mg/kg) administered accordingly to the same “binge” schedule (4 administrations, 2 hours apart) is able to induce toxicity on 5-HT and DA innervations. Indeed, 3 and 7 days following the last METH administration we reported a loss of DAergic and 5-HTergic terminals measured by means of immunohistochemical detection of their transporters (5-HTT and DAT) [46]. Moreover, this model of METH administration (4×10 mg/kg, 2 h apart) is currently the most frequently used rat model of METH neurotocivity, and is associated with striatal dopamine and serotonin depletion, hyperthermia and high mortality [7].…”

Section: Discussionmentioning

confidence: 87%

Δ9-Tetrahydrocannabinol Prevents Methamphetamine-Induced Neurotoxicity

et al. 2014

Self Cite

View full text Add to dashboard Cite

Methamphetamine (METH) is a potent psychostimulant with neurotoxic properties. Heavy use increases the activation of neuronal nitric oxide synthase (nNOS), production of peroxynitrites, microglia stimulation, and induces hyperthermia and anorectic effects. Most METH recreational users also consume cannabis. Preclinical studies have shown that natural (Δ9-tetrahydrocannabinol, Δ9-THC) and synthetic cannabinoid CB1 and CB2 receptor agonists exert neuroprotective effects on different models of cerebral damage. Here, we investigated the neuroprotective effect of Δ9-THC on METH-induced neurotoxicity by examining its ability to reduce astrocyte activation and nNOS overexpression in selected brain areas. Rats exposed to a METH neurotoxic regimen (4×10 mg/kg, 2 hours apart) were pre- or post-treated with Δ9-THC (1 or 3 mg/kg) and sacrificed 3 days after the last METH administration. Semi-quantitative immunohistochemistry was performed using antibodies against nNOS and Glial Fibrillary Acidic Protein (GFAP). Results showed that, as compared to corresponding controls (i) METH-induced nNOS overexpression in the caudate-putamen (CPu) was significantly attenuated by pre- and post-treatment with both doses of Δ9-THC (−19% and −28% for 1 mg/kg pre- and post-treated animals; −25% and −21% for 3 mg/kg pre- and post-treated animals); (ii) METH-induced GFAP-immunoreactivity (IR) was significantly reduced in the CPu by post-treatment with 1 mg/kg Δ9-THC1 (−50%) and by pre-treatment with 3 mg/kg Δ9-THC (−53%); (iii) METH-induced GFAP-IR was significantly decreased in the prefrontal cortex (PFC) by pre- and post-treatment with both doses of Δ9-THC (−34% and −47% for 1 mg/kg pre- and post-treated animals; −37% and −29% for 3 mg/kg pre- and post-treated animals). The cannabinoid CB1 receptor antagonist SR141716A attenuated METH-induced nNOS overexpression in the CPu, but failed to counteract the Δ9-THC-mediated reduction of METH-induced GFAP-IR both in the PFC and CPu. Our results indicate that Δ9-THC reduces METH-induced brain damage via inhibition of nNOS expression and astrocyte activation through CB1-dependent and independent mechanisms, respectively.

show abstract

Section: Discussionmentioning

confidence: 87%

Δ9-Tetrahydrocannabinol Prevents Methamphetamine-Induced Neurotoxicity

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, differentiating preexisting deficits from methamphetamine-induced cognitive deficits poses significant challenges (Dean et al, 2013), and concerns regarding the interpretation of these discrepancies and their clinical significance have been raised (Hart et al, 2012). Despite this, the preponderance of evidence from preclinical, cross-sectional human, and brain imaging studies supports the assertion that methamphetamine abuse does indeed cause cognitive decline in at least some individuals (i.e., individuals at the age of early-to-middle adulthood; Dean et al, 2013) and that some cognitive/behavioral changes may be the result of methamphetamine neurotoxicity (Bortolato et al, 2009). Further, individual difference variables such as age, education level, and genotype appear to moderate the relationship between methamphetamine use and cognitive deficits (Dean et al., 2013).…”

Section: Neurocognitive Functioning Associated With Chronic Methammentioning

confidence: 99%

Methamphetamine: An update on epidemiology, pharmacology, clinical phenomenology, and treatment literature

Courtney

Ray

2014

Drug and Alcohol Dependence

367

255

View full text Add to dashboard Cite

Background-Despite initial reports of a decline in use in the early 2000s, methamphetamine remains a significant public health concern with known neurotoxic and neurocognitive effects to the user. The goal of this review is to update the literature on methamphetamine use and addiction since its assent to peak popularity in 1990s.Methods-Specifically, we first review recent epidemiological reports with a focus on methamphetamine accessibility, changes in use and disorder prevalence rates over time, and accurate estimates of the associated burden of care to the individual and society. Second, we review methamphetamine pharmacology literature with emphasis on the structural and functional neurotoxic effects associated with repeated use of the drug. Third, we briefly outline the findings on methamphetamine-related neurocognitive deficits as assessed via behavioral and neuroimaging paradigms. Lastly, we review the clinical presentation of methamphetamine addiction and the evidence supporting the available psychosocial and pharmacological treatments within the context of an addiction biology framework.Conclusion-Taken together, this review provides a broad-based update of the available literature covering methamphetamine research over the past two decades and concludes with recommendations for future research.

show abstract

“…Similar to prior studies (Bortolato et al, 2009a), mice (8 per genotype) were individually exposed to two identical novel objects, affixed to the floor and symmetrically placed 6 cm from the two nearest walls of a cubed Plexiglas box (20 Â 20 Â 20 cm 3 ) lit to 120 lux. Mice were placed in a corner facing the center, equidistant from each object, with the starting position rotated and counter-balanced for genotype.…”

Section: Novel Object Interaction and Recognitionmentioning

confidence: 99%

Sociocommunicative and Sensorimotor Impairments in Male P2X4-Deficient Mice

Wyatt

Godar

Khoja

et al. 2013

Neuropsychopharmacol

Self Cite

View full text Add to dashboard Cite

Purinergic P2X receptors are a family of ligand-gated ion channels gated by extracellular adenosine 5'-triphosphate (ATP). Of the seven P2X subtypes, P2X4 receptors (P2X4Rs) are richly expressed in the brain, yet their role in behavioral organization remains poorly understood. In this study, we examined the behavioral responses of P2X4R heterozygous (HZ) and knockout (KO) mice in a variety of testing paradigms designed to assess complementary aspects of sensory functions, emotional reactivity, and cognitive organization. P2X4R deficiency did not induce significant alterations of locomotor activity and anxiety-related indices in the novel open field and elevated plus-maze tests. Conversely, P2X4R KO mice displayed marked deficits in acoustic startle reflex amplitude, as well as significant sensorimotor gating impairments, as assessed by the prepulse inhibition of the startle. In addition, P2X4R KO mice displayed enhanced tactile sensitivity, as signified by a lower latency in the sticky-tape removal test. Moreover, both P2X4R HZ and KO mice showed significant reductions in social interaction and maternal separation-induced ultrasonic vocalizations in pups. Notably, brain regions of P2X4R KO mice exhibited significant brain-regional alterations in the subunit composition of glutamate ionotropic receptors. These results collectively document that P2X4-deficient mice exhibit a spectrum of phenotypic abnormalities partially akin to those observed in other murine models of autism-spectrum disorder. In conclusion, our findings highlight a putative role of P2X4Rs in the regulation of perceptual and sociocommunicative functions and point to these receptors as putative targets for disturbances associated with neurodevelopmental disorders.

show abstract

Methamphetamine Induces Long-Term Alterations in Reactivity to Environmental Stimuli: Correlation with Dopaminergic and Serotonergic Toxicity

Cited by 16 publications

References 73 publications

Δ9-Tetrahydrocannabinol Prevents Methamphetamine-Induced Neurotoxicity

Δ9-Tetrahydrocannabinol Prevents Methamphetamine-Induced Neurotoxicity

Methamphetamine: An update on epidemiology, pharmacology, clinical phenomenology, and treatment literature

Sociocommunicative and Sensorimotor Impairments in Male P2X4-Deficient Mice

Contact Info

Product

Resources

About