scholarly journals Mitochondrial function influences expression of methamphetamine-induced behavioral sensitization

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
I. Daphne Calma ◽  
Amanda L. Persons ◽  
T. Celeste Napier
Keyword(s):  
Mitochondrial Function ◽  
Behavioral Sensitization ◽  
High Energy ◽  
Behavioral Changes ◽  
Energy Requirements ◽  
Self Administration ◽  
Methamphetamine Use ◽  
Laboratory Rats ◽  
Mitochondrial Toxin ◽  
Brain Changes

AbstractRepeated methamphetamine use leads to long lasting brain and behavioral changes in humans and laboratory rats. These changes have high energy requirements, implicating a role for mitochondria. We explored whether mitochondrial function underpins behaviors that occur in rats months after stopping methamphetamine self-administration. Accordingly, rats self-administered intravenous methamphetamine for 3 h/day for 14 days. The mitochondrial toxin rotenone was administered as (1 mg/kg/day for 6 days) via an osmotic minipump starting at 0, 14 or 28 days of abstinence abstinence. On abstinence day 61, expression of methamphetamine-induced behavioral sensitization was obtained with an acute methamphetamine challenge in rotenone-free rats. Rotenone impeded the expression of sensitization, with the most robust effects obtained with later abstinence exposure. These findings verified that self-titration of moderate methamphetamine doses results in behavioral (and thus brain) changes that can be revealed months after exposure termination, and that the meth-initiated processes progressed during abstinence so that longer abstinence periods were more susceptible to the consequences of exposure to a mitochondrial toxin.

scholarly journals Mitochondrial Function Influences Expression of Methamphetamine-Induced Motor Sensitization

2021 ◽  
Author(s):  
I. Daphne Calma ◽  
Amanda L. Persons ◽  
T. Celeste Napier
Keyword(s):  
Mitochondrial Function ◽  
Neuronal Plasticity ◽  
Acute Treatment ◽  
Low Dose ◽  
High Energy ◽  
Energy Requirements ◽  
Self Administration ◽  
Osmotic Minipump ◽  
Methamphetamine Use ◽  
Administration Protocol

Abstract Repeated methamphetamine use leads to neuronal maladaptations resulting in addictions. Mechanisms that underpin such adaptations have high energy requirements, implicating mitochondria involvement in addiction-related processes. We pharmacologically explored this possibility in methamphetamine self-administering rats. Motor sensitization a readout that is thought to reflect brain maladaptations akin to those occurring in methamphetamine abusing humans. This was assessed to determine (i) if a short access self-administration protocol results in the expression of motor sensitization, (iii) if and when, mitochondrial function is critical for protracted maintenance and (iii) whether drug contingency influences motor sensitization. Rats self-administered iv methamphetamine for 3 hours per day for 14 days. Those with iv cannula that failed patency were redeployed as non-contingent methamphetamine-matched animals. At three different times during forced abstinence, mitochondrial function was impaired with a low dose of the toxin, rotenone (1mg/kg/day) via a osmotic minipump. Motor sensitization was determined during an acute treatment of methamphetamine (1.25mg/kg sc) on abstinence day 62. Methamphetamine self-administration was sufficient to induce motor sensitization. Rotenone administration prevented the expression of sensitization, but the profile depended on abstinence time exposure. Drug contingency also influenced sensitization profiles. Mitochondrial function underpins neuronal plasticity associated with maintenance of motor sensitization induced by methamphetamine self-administration.

scholarly journals Parkin regulates drug-taking behavior in rat model of methamphetamine use disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Akhil Sharma ◽  
Arman Harutyunyan ◽  
Bernard L. Schneider ◽  
Anna Moszczynska
Keyword(s):  
Neural Substrates ◽  
Genetically Engineered ◽  
Wild Type ◽  
Therapeutic Approaches ◽  
Self Administration ◽  
Methamphetamine Use ◽  
New Therapeutic Approaches ◽  
Extended Access ◽  
High Doses ◽  
Methamphetamine Use Disorder

AbstractThere is no FDA-approved medication for methamphetamine (METH) use disorder. New therapeutic approaches are needed, especially for people who use METH heavily and are at high risk for overdose. This study used genetically engineered rats to evaluate PARKIN as a potential target for METH use disorder. PARKIN knockout, PARKIN-overexpressing, and wild-type young adult male Long Evans rats were trained to self-administer high doses of METH using an extended-access METH self-administration paradigm. Reinforcing/rewarding properties of METH were assessed by quantifying drug-taking behavior and time spent in a METH-paired environment. PARKIN knockout rats self-administered more METH and spent more time in the METH-paired environment than wild-type rats. Wild-type rats overexpressing PARKIN self-administered less METH and spent less time in the METH-paired environment. PARKIN knockout rats overexpressing PARKIN self-administered less METH during the first half of drug self-administration days than PARKIN-deficient rats. The results indicate that rats with PARKIN excess or PARKIN deficit are useful models for studying neural substrates underlying “resilience” or vulnerability to METH use disorder and identify PARKIN as a novel potential drug target to treat heavy use of METH.

Intraventricular self-administration of leucine-enkephalin by laboratory rats

Life Sciences ◽  
1982 ◽  
Vol 31 (15) ◽  
pp. 1527-1530 ◽  
Author(s):  
Brian R. Smith ◽  
Zavie W. Brown ◽  
Zalman Amit
Keyword(s):  
Self Administration ◽  
Leucine Enkephalin ◽  
Laboratory Rats

Behavioral Effects of Prenatal and Adult Exposure To Toxic Chemicals Found in Lake Ontario Fish: Two Methodological Approaches

1996 ◽  
Vol 12 (3-4) ◽  
pp. 419-426 ◽  
Author(s):  
Helen Daly ◽  
Thomas Darvill ◽  
Edward Lonky ◽  
Jacqueline Reihman ◽  
David Sargent
Keyword(s):  
Human Subjects ◽  
Lake Ontario ◽  
Behavioral Changes ◽  
Laboratory Rats ◽  
Confounding Variables ◽  
Correlational Method ◽  
And Behavior ◽  
And Control ◽  
Adult Exposure ◽  
To Receive

Two research approaches are described that were used to determine behavioral changes following a diet of Lake Ontario fish. Approach 1 involved the correlational method, in which human subjects voluntarily ate contaminated Lake Ontario fish. Demographic information, data on the amount of Lake Ontario fish consumed, and control variables were obtained during an interview. Respondents' behavior, as well as the behavior of their children, then was measured. Because subjects were not assigned randomly to eat or not eat Lake Ontario fish, other variables that might have influenced both consumption of fish and behavior had to be considered. Therefore, confounding variables were measured and their influence controlled for using statistical techniques. Approach 2 involved the experimental method using laboratory rats, where subjects were assigned randomly to receive a diet of environmentally contaminated Lake Ontario salmon, relatively uncontaminated Pacific Ocean salmon, or no salmon. Since the rats fed Lake Ontario salmon behaved differently than the other two groups on nine tasks, it was concluded that the contaminants in Lake Ontario salmon caused behavioral changes. Random assignment of subjects to groups eliminated competing explanations. If similar behavioral (e.g., emotional or cognitive) results were obtained using the two approaches, then the results utilizing rats probably could be generalized to humans, and the correlational results found in humans probably were due to a cause and effect relationship.

Post-Traumatic Stress Disorder

2020 ◽  
pp. 433-464
Author(s):  
Richard McCarty
Keyword(s):  
Animal Models ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Behavioral Changes ◽  
Laboratory Animals ◽  
Nasal Administration ◽  
Post Traumatic Stress ◽  
Laboratory Rats ◽  
Post Traumatic

Two especially valuable animal models of post-traumatic stress disorder (PTSD) have been developed, including brief exposure of laboratory rats to a predator (a cat) or its odor, and the single prolonged stress paradigm. In each of these models, laboratory animals are evaluated for behavioral changes several days to several weeks following the stressful experience and are compared to unstressed controls. In both of these models, stressed animals display behavioral changes consistent with a PTSD-like phenotype. Using these models, investigators have explored central and peripheral neural and endocrine changes associated with the onset of PTSD-like symptoms and approaches to prevent or block the effects of the traumatic stressor on behavioral changes. Two particularly effective treatments that have been described include administration of a protein synthesis inhibitor and intra-nasal administration of neuropeptide Y. Animal models also provide an opportunity to study transgenerational transmission of PTSD risk.

Substance use disorders and the mechanisms of drug addiction

2020 ◽  
pp. 477-491
Author(s):  
Trevor W. Robbins ◽  
Barry J. Everitt
Keyword(s):  
Drug Addiction ◽  
Positive Reinforcement ◽  
Animal Studies ◽  
Dorsal Striatum ◽  
Critical Issue ◽  
Neural Substrates ◽  
Future Prospects ◽  
Self Administration ◽  
Limbic Systems ◽  
Brain Changes

The understanding of drug addiction has gained much from a neuroscientific approach, reflected by changing approaches in diagnosis. The two main psychological accounts of addiction to substances, ranging from alcohol and nicotine to opioids and stimulant drugs, are opponent motivational processing, emphasizing the importance of withdrawal symptoms, and aberrant learning from positive reinforcement. The neural and neurochemical systems implicated have been identified on the basis of animal studies, using especially the self-administration paradigm, and human investigations employing a range of brain imaging modalities. These neural substrates include dopamine-dependent functions of the ventral and dorsal striatum, as well as regulatory influences of fronto-limbic systems. The chapter considers the critical issue of cause and effect, and whether brain changes reflect neurotoxic effects of abuse or whether there are predisposing neurobehavioural factors. It also outlines the current situation and future prospects for treatment by medication, possibly in association with psychological approaches.

Evaluation of Mitochondrial Function in Isolated Rat Hepatocytes and Mitochondria during Oxidative Stress

2007 ◽  
Vol 35 (3) ◽  
pp. 353-361 ◽  
Author(s):  
Zuzana Červinková ◽  
Halka Lotková ◽  
Pavla Křivaková ◽  
Tomáš Roušar ◽  
Otto Kučera ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Mitochondrial Permeability Transition ◽  
Energy Requirement ◽  
High Energy ◽  
Molecular Probe ◽  
Isolated Rat Hepatocytes ◽  
Isolated Mitochondria

The majority of toxic agents act either fully or partially via oxidative stress, the liver, specifically the mitochondria in hepatocytes, being the main target. Maintenance of mitochondrial function is essential for the survival and normal performance of hepatocytes, which have a high energy requirement. Therefore, greater understanding of the role of mitochondria in hepatocytes is of fundamental importance. Mitochondrial function can be analysed in several basic models: hepatocytes cultured in vitro; mitochondria in permeabilised hepatocytes; and isolated mitochondria. The aim of our study was to use all of these approaches to evaluate changes in mitochondria exposed in vitro to a potent non-specific peroxidating agent, tert-butylhydroperoxide (tBHP), which is known to induce oxidative stress. A decrease in the mitochondrial membrane potential (MMP) was observed in cultured hepatocytes treated with tBHP, as illustrated by a significant reduction in Rhodamine 123 accumulation and by a decrease in the fluorescence of the JC-1 molecular probe. Respiratory Complex I in the mitochondria of permeabilised hepatocytes showed high sensitivity to tBHP, as documented by high-resolution respirometry. This could be caused by the oxidation of NADH and NADPH by tBHP, followed by the disruption of mitochondrial calcium homeostasis, leading to the collapse of the MMP. A substantial decrease in the MMP, as determined by tetraphenylphosphonium ion-selective electrode measurements, also confirmed the dramatic impact of tBHP-induced oxidative stress on mitochondria. Swelling was observed in isolated mitochondria exposed to tBHP, which could be prevented by cyclosporin A, which is evidence for the role of mitochondrial permeability transition. Our results demonstrate that all of the above-mentioned models can be used for toxicity assessment, and the data obtained are complementary.

scholarly journals Characterization of the Agricultural Supply of Desalinated Seawater in Southeastern Spain

Water ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1233 ◽  
Author(s):  
Victoriano Martínez-Alvarez ◽  
Jose F. Maestre-Valero ◽  
Manuel J. González-Ortega ◽  
Belén Gallego-Elvira ◽  
Bernardo Martin-Gorriz
Keyword(s):  
Socioeconomic Development ◽  
High Energy ◽  
Water Sources ◽  
Irrigation District ◽  
Energy Requirements ◽  
Irrigated Agriculture ◽  
Seawater Desalination ◽  
Alternative Source ◽  
Production And Distribution ◽  
Desalination Plants

The increasing shortage of water for crop irrigation in arid and semiarid regions is encouraging the use of non-conventional resources. In the last decade, seawater desalination has consolidated its position as an alternative source to increase the supply for agricultural irrigation in Spain and Israel, where the farmers’ acceptance is progressively rising, despite the supply price being much higher than that of other conventional water sources. This article describes the current situation of desalinated seawater production and supply to agriculture in the southeast of Spain, and analyzes key questions such as its role in regional water planning, the infrastructure needed for conveyance and distribution, the energy requirements, the production and distribution costs, and the final price to farmers. The study is based on descriptive and quantitative data collected from desalination plants and irrigation district managers through technical questionnaires and personal interviews. The results show how seawater desalination is effectively alleviating the regional constraints in the irrigated agriculture supply, and why it is becoming strategic to maintaining food production and socioeconomic development. However, the high-energy requirements and associated costs in comparison with other water sources limit a more widespread use for agriculture, and for this reason desalinated water still only plays a complementary role in most irrigation districts.

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