Browsing by Author "Janetsian, Sarine S."

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    Evaluating Differences in Cognitive Function after N-Acetyl-Cysteine Treatment in a Two-Hit Rat Model of Schizophrenia
    (Office of the Vice Chancellor for Research, 2014-04-11) Cayetano, Nadalie K. J.; Janetsian, Sarine S.; Lapish, Christopher C.
    Schizophrenia (SZ) is a chronic mental disorder characterized by positive and negative symptoms both of which impair normal functioning. Effective treatment options for negative and cognitive symptoms are non-existent. Identifying translational biomarkers that can be applied across species could aid drug development. Remediation of cognitive impairments will be assessed after administering N-Acetyl-Cysteine (NAC) by the use of validated measures of cognitive performance in a “two-hit” model of SZ. Pups of Sprague Dawley dams were used. Each litter was split into two groups: maternally deprived (MD) or sham. The MD group (n= 9) were weighed and removed from their mothers for 24 hours on post-natal day 9. MD acts as an early-life stressor and may be linked with the development of SZ. The sham group (n= 9) served as controls. On post-natal day 75-88, MD rats (n= 9) received an injection of NAC (90.0 mg/kg; n= 5) or saline (n= 4). All sham rats received saline. Two days after NAC treatment, all rats received an acute injection of Phencyclidine (PCP) at 2.0 mg/kg, an N-Methyl-D-Aspartate antagonist. PCP alters glutamatergic signaling and is the second model used to induce SZ. The day after injection, short-term memory was assessed using temporal order and novel object recognition tasks. The same tasks were given to assess alterations of glutamatergic signaling after receiving chronic 2.0 mg/kg of PCP injections for six days. Preliminary results indicate no detectable differences in temporal order and novel object recognition tasks between the MD groups who received NAC from those who received saline. No significant differences were found between the MD and sham groups that received saline. Furthermore, there were no differences between any of the groups after chronic PCP administration. Additional animals are being tested to increase group sizes and to have larger power when running the analyses.
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    Memory impairment and alterations in prefrontal cortex gamma band activity following methamphetamine sensitization
    (Springer-Verlag, 2015-06) Janetsian, Sarine S.; Linsenbardt, David N.; Lapish, Christopher C.; Department of Psychology, School of Science
    RATIONALE: Repeated methamphetamine (MA) use leads to increases in the incentive motivational properties of the drug as well as cognitive impairments. These behavioral alterations persist for some time following abstinence, and neuroadaptations in the structure and function of the prefrontal cortex (PFC) are particularly important for their expression. However, there is a weak understanding of the changes in neural firing and oscillatory activity in the PFC evoked by repeated drug use, thus complicating the development of novel treatment strategies for addiction. OBJECTIVES: The purpose of the current study was to assess changes in cognitive and brain function following MA sensitization. METHODS: Sensitization was induced in rats, then temporal and recognition memory were assessed after 1 or 30 days of abstinence. Electrophysiological recordings from the medial PFC were also acquired from rats whereupon simultaneous measures of oscillatory and spiking activity were examined. RESULTS: Impaired temporal memory was observed after 1 and 30 days of abstinence. However, recognition memory was only impaired after 1 day of abstinence. An injection of MA profoundly decreased neuronal firing rate and the anesthesia-induced slow oscillation (SO) in both sensitized (SENS) and control (CTRL) rats. Strong correlations were observed between the SO and gamma band power, which was altered in SENS animals. A decrease in the number of neurons phase-locked to the gamma oscillation was also observed in SENS animals. CONCLUSIONS: The changes observed in PFC function may play an integral role in the expression of the altered behavioral phenotype evoked by MA sensitization.
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    Methamphetamine-induced deficits in social interaction are not observed following abstinence from single or repeated exposures
    (Wolters Kluwer, 2015-12) Janetsian, Sarine S.; McCane, Aqilah M.; Linsenbardt, David N.; Lapish, Christopher C.; Department of Psychology, School of Science
    The purpose of the current study was to assess social interaction (SI) following acute and repeated methamphetamine (MA) administration. Rats were injected with 5.0 mg/kg of MA and SI was tested 30 minutes or 24 hours later. In another group of animals, MA sensitization was induced using 5.0 mg/kg of MA, and SI was assessed after one day or thirty days of abstinence. SI was reduced in rats injected with MA 30 minutes, but not 24 hours, prior to testing, compared with saline controls. Impaired SI was observed in combination with active avoidance of the conspecific animal. Repeated injections of MA progressively reduced locomotor activity and increased stereotypy, indicating that animals were sensitized. However, no differences in SI were observed 24 hours or 30 days following the induction of sensitization. The absence of detectable differences in SI following MA sensitization may be attributable to the relatively short regimen used to induce sensitization. However, the current series of experiments provides evidence that an acute injection of MA decreases SI and simultaneously increases avoidance behavior, which supports a link between psychostimulant use and impaired social functioning. These data suggest that the acute injection model may provide a useful model to explore the neural basis of impaired social functioning and antisocial behavior.