ABSTRACT
Although animal models cannot broadly represent uniquely human psychiatric or psychological syndromes such as anxiety, depression, or schizophrenia, behavioral testing in rodents can be extremely helpful to investigate specific disease aspects and symptoms. Animal behavioral test batteries allow researchers to reveal specific behavioral changes in genetically modified mice or following targeted treatments or in response to environmental interventions. Examples of types of behaviors that can be combined in a test battery include anxiety-like behavior, learning and memory, depression-relevant behavior, social interaction, and locomotor hyperactivity. Here, we describe several commonly used and relatively simple behavioral tests which can be combined in the same cohort of animals.
Subject(s)
Behavior Rating Scale , Behavior, Animal , Animals , Mice , Humans , Behavior, Animal/physiology , Rodentia , Memory , Anxiety , Disease Models, AnimalABSTRACT
The val66met polymorphism of the brain-derived neurotrophic factor (BDNF) gene has been identified as a potential moderator for the relationship between chronic stress and executive functioning. However, whether the presence of the met allele increases cognitive vulnerability or resilience to stress has yet to be determined. Given the established effects of autonomic activity and psychological arousal on executive functioning, in the present study, 56 healthy university students completed self-report measures of chronic stress, positive arousal (vigour) and negative arousal (anxiety) and measured heart-rate variability to quantify autonomic activity. Participants then completed a cognitive test battery that measured attention, decision-making, visual learning and working memory. Regression analyses demonstrated that Val/met participants performed better on attention and working memory tasks than Val/val participants, but no differences were seen in decision-making and visual learning. Further, Val/met participants were protected from stress-related differences in attention seen in Val/val participants. Val66met was not associated with physiological or psychological arousal. This study demonstrates that val66met plays an important but selective role in cognitive performance.
ABSTRACT
Chronic methamphetamine (Meth) abuse may induce psychosis similar to that observed in schizophrenia. Brain-derived neurotrophic factor (BDNF) has been implicated in the development of psychosis. We have previously shown long-term protein expression changes in mice treated chronically with Meth depending on BDNF Val66Met genotype. The aim of this study was to investigate if these protein expression changes were associated with differential changes in a range of behavioural paradigms for cognition, anxiety, social and other behaviours. Male and female Val/Val, Val/Met and Met/Met mice were treated with an escalating Meth dose protocol from 6 to 9 weeks of age, with controls receiving saline injections. Several overlapping cohorts were tested in the Y-maze for short-term spatial memory, novel-object recognition test, context and cued fear conditioning, sociability and social preference, elevated plus maze for anxiety-like behaviour and prepulse inhibition (PPI) of acoustic startle. Finally, the animals were assessed for spontaneous exploratory locomotor activity and acute Meth-induced locomotor hyperactivity. Acute Meth caused significantly greater locomotor hyperactivity in mice previously treated with the drug than in saline-pretreated controls. Meth-pretreated female mice showed a mild increase in spontaneous locomotor activity. There were no Meth-induced deficits in any of the other behavioural tests. Val/Met mice showed higher overall social investigation time and lower PPI compared with the Val/Val genotype independent of pretreatment. These results show limited long-term effects of chronic Meth on a range of cognitive, affective and social behaviours despite marked drug-induced locomotor sensitization in mice. There was no interaction with BDNF Val66Met genotype.
Subject(s)
Amphetamine-Related Disorders , Methamphetamine , Mice , Male , Female , Animals , Methamphetamine/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , Genotype , Social Behavior , CognitionABSTRACT
The val66met polymorphism of the brain-derived neurotrophic factor gene has been associated with changes in components of executive functioning such as decision making; however, this relationship remains unclear. Val66met-related changes in attention and visual processing speed may explain potential changes in decision making. Furthermore, chronic stress disrupts executive functions and alters autonomic activity. Because the relationship between val66met and cognition has not been investigated in the context of chronic stress or stress-related autonomic changes, in this study 55 healthy university students completed self-report measures of chronic stress and mental health. Participants then completed a virtual reality cognitive test battery (CONVIRT) measuring decision making, attention, and visual processing reaction times. To measure autonomic activity, saliva alpha amylase and heart rate variability (HRV) were assessed at baseline and after CONVIRT testing. Saliva samples were used to identify val66met genotype. Regression analyses demonstrated that val66met was the strongest predictor of decision making and attention, but not visual processing, where valine/methionine (Val/met) participants had faster reaction times than Val/val participants. Val/met participants also had higher perceived chronic stress and heightened increases in sympathetic activity, but not parasympathetic activity. Neither stress nor autonomic activity moderated the effect of val66met on decision making or attention. This study is the first to investigate the role of val66met in decision making, attention, and visual processing while taking into account chronic stress and autonomic activity. This multifactorial approach revealed that carriers of the Val/met genotype may have better decision making and attention than Val/val carriers.
