Effects of a methamphetamine vaccine, IXT-v100, on methamphetamine-related behaviors

Mitochondrial dysfunction and autophagy activation are associated with cardiomyopathy developed by extended methamphetamine self-administration in rats

“…Both control and METH self-administration rats were free-fed until they reached a minimum body weight of 390 g for males and 290 g for females. The rats were then maintained at 85–90% of their free-feeding body weights (approximately 330 g for males and 245 g for females) with free access to water, as reported earlier [ 35 , 38 ]. The rats were fed once per day in the self-administration chamber similar to that while in their home cages (14 g of food, standard rodent chow, Harlan Teklad, Madison, WI, USA).…”

“…Each rat was implanted with a chronic indwelling jugular catheter to intravenously self-administer METH as described previously [ 35 , 37 , 38 , 41 ]. Control rats were paired with METH rats in a yoked saline control paradigm.…”

“…Each experimental chamber contained two response levers mounted on one wall of the chamber, and a stimulus light was located above each lever. METH rats were trained to self-administer METH by pressing one of the response levers (i.e., the “active” lever) under a fixed-ratio 1 (FR1) reinforcement schedule [ 38 ]. Depression on the inactive lever resulted in no programmed consequences.…”

“…However, a more realistic representation of the use of METH in people afflicted with METH addiction is ‘binge and crash’ which is characterized by long, repeated binges of METH use, often without food or sleep, followed by periods of abstinence or sleep, often referred to as a crash [ [32] , [33] , [34] ]. Recent development of a rodent model which more closely resembles aspects of human METH use allows for extended access self-administration of METH resulting in an escalation of drug intake and brain METH levels in rats comparable to that of people chronically using METH [ [35] , [36] , [37] , [38] ]. Therefore, the aim of the present study was to determine the molecular, functional, and pathological events associated with the development of cardiomyopathy in the model of rodent self-administration of METH.…”

“…Therefore, the aim of the present study was to determine the molecular, functional, and pathological events associated with the development of cardiomyopathy in the model of rodent self-administration of METH. In the present study, we have utilized our previously reported METH self-administered rat models mimicking the human METH addiction pattern to determine the molecular events associated with METH cardiomyopathy using integrated and complementary gravimetric, morphometric, histological, gene expression, and longitudinal echocardiographic studies [ 35 , 38 , 39 ]. We employed transmission electron microscopic observations, electron transport system, metabolic and autophagy process associated proteins expression analysis, native gel electrophoresis, and enzymatic metabolic assays to dissect molecular underpinnings associated with the development of METH-cardiomyopathy following self-administration of METH in rats.…”