Individual responses to novelty are associated with differences in behavioral and neurochemical profiles

Department of Pharmacology, Medical School, University of Ioannina, 45110 Ioannina, Greece.
Behavioural Brain Research (Impact Factor: 3.03). 04/2008; 187(2):462-72. DOI: 10.1016/j.bbr.2007.10.010
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ABSTRACT Experimental animals can be differentiated on the basis of their horizontal or vertical activity to high responders (HR) and low responders (LR) upon exposure to a novel environment. These individual differences have been associated with behavioral and neurobiological differences in a number of experimental procedures used for studying sensitivity to psychostimulants, anxiety, depression, and cognitive function. In the present study, we differentiated the rats to HR and LR based on their vertical activity upon exposure to a novel environment. Additionally, we ascertained whether HR and LR rats differ in a battery of tests such as passive avoidance (PA), object recognition (OR), and the water-maze (WM) that provide indices for cognitive function and the forced swim test (FST), an animal model of affective responsivity and antidepressant-like activity. Potential differences in neurochemical indices between the two phenotypes were also examined. HR rats displayed impaired non-spatial object recognition memory, but enhanced spatial performance, as compared to LR rats. FST induced "depressive-like" symptoms in both phenotypes that were differently manifested in HR versus LR rats. Neurochemical findings revealed distinct differences in serotonergic and dopaminergic activity in the striatum and the prefrontal cortex of HR as compared to LR rats. The above results show that HR and LR rats exhibit important differences in a battery of tests related to cognitive performance or affective responsivity, which may be associated with differences in certain neurobiological parameters.

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Available from: Zeta Papadopoulou-Daifoti, Sep 29, 2015
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    • "Interestingly, behavioral habituation as assessed by measuring motor activity was improved in CB1R knockout mice (Degroot et al., 2005). Habituation can be used as a model of non-associative learning and memory that reflects the organization of behavioral output (Thiel et al., 1998; Mogensen et al., 2003; Antoniou et al., 2008; Polissidis et al., 2010). In this context, novel findings regarding cannabinoids' effects on non-associative learning and memory will provide additional and important information on their role in modulating distinct features of cognition. "
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    ABSTRACT: Endogenous and exogenous cannabinoids modulate learning and memory primarily via the cannabinoid type 1 receptor (CB1R). A variety of experimental procedures has focused on the role of CB1R in various aspects of learning and memory processes. However, the picture still remains unclear as there is a lack of information on the effects of relatively low doses of CB1R agonists in relation to their effects on locomotion. The present study sought to investigate CB1R activation, using a range of relatively low doses of the CB1R agonist WIN55,212-2, on multiple aspects of learning and memory in rats. For this purpose, non-associative learning was examined using the habituation of locomotion paradigm, recognition memory was evaluated with the novel object recognition task, and the radial water maze test was selected to assess rats’ spatial memory. The ability of the CB1R antagonist, SR141716A, to counteract WIN55,212-2-induced behavioral effects was also tested. WIN55,212-2 (0.3, but not 0.03 or 0.1 mg/kg) disrupted non-associative learning, different aspects of short- and long-term recognition memory (storage and retrieval) and retention of spatial memory. The 0.3 mg/kg dose of WIN55,212-2 also decreased ambulatory, but not vertical (rearing), activity in non-habituated rats. These effects appeared to be CB1R dependent since pretreatment with SR141716A (0.03 mg/kg) prevented the WIN55,212-2-induced behavioral effects. The present findings further support and extend the complex impact of exogenous cannabinoids on learning and memory in relation to their effects on locomotion.
    Pharmacology Biochemistry and Behavior 09/2014; 124:58–66. DOI:10.1016/j.pbb.2014.05.014 · 2.78 Impact Factor
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    • "The original classification into HR/LR animals by Piazza et al. (1989) used a circular corridor with photocells counting locomotor activity in a novel environment and the animals were then divided by a median split (Piazza et al., 1989). Others have used locomotion (Hooks et al., 1991), or rearing and sniffing in the air in an open field arena to classify the activity (Antoniou et al., 2008). By only measuring locomotor activity it may be difficult to interpret the behavior, for example whether increased activity is related to the rats' intention to explore or to search for an escape route. "
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    ABSTRACT: Certain personality types and behavioral traits display high correlations to drug use and an increased level of dopamine in the reward system is a common denominator of all drugs of abuse. Dopamine response to drugs has been suggested to correlate with some of these personality types and to be a key factor influencing the predisposition to addiction. This study investigated if behavioral traits can be related to potassium- and amphetamine-induced dopamine response in the dorsal striatum, an area hypothesized to be involved in the shift from drug use to addiction. The open field and multivariate concentric square field™ tests were used to assess individual behavior in male Wistar rats. Chronoamperometric recordings were then made to study the potassium- and amphetamine-induced dopamine response in vivo. A classification based on risk-taking behavior in the open field was used for further comparisons. Risk-taking behavior was correlated between the behavioral tests and high risk takers displayed a more pronounced response to the dopamine uptake blocking effects of amphetamine. Behavioral parameters from both tests could also predict potassium- and amphetamine-induced dopamine responses showing a correlation between neurochemistry and behavior in risk-assessment and risk-taking parameters. In conclusion, the high risk-taking rats showed a more pronounced reduction of dopamine uptake in the dorsal striatum after amphetamine indicating that this area may contribute to the sensitivity of these animals to psychostimulants and proneness to addiction. Further, inherent dopamine activity was related to risk-assessment behavior, which may be of importance for decision-making and inhibitory control, key components in addiction.
    Frontiers in Behavioral Neuroscience 07/2014; 8:236. DOI:10.3389/fnbeh.2014.00236 · 3.27 Impact Factor
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    • "Thus, the study of individual differences in behavioral traits allows the identification of relevant information concerning such influencing factors [6]. The individual differences approach has been used, for example, to study critical elements underlying the development of anxiety-and depressionlike disorders [7] [8] [9] [10] [11]. "
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    ABSTRACT: Individual differences in the forced swimming test (FST) could be associated with differential temporal dynamics of gene expression and neurotransmitter activity. We tested juvenile male rats in the FST and classified the animals into those with low and high immobility according to the amount of immobility time recorded in FST. These groups and a control group which did not undergo the FST were sacrificed either one, six or twenty-four hours after the test. We analyzed the expression of the CRF, CRFR1, BDNF and TrkB in the prefrontal cortex, hippocampus and nucleus accumbens as well as norepinephrine, dopamine, serotonin, glutamate, GABA and glutamine in the hippocampus and nucleus accumbens. Animals with low immobility showed significant reductions of BDNF expression across time points in both the prefrontal cortex and the nucleus accumbens when compared with non-swim control. Moreover, rats with high immobility only showed a significant decrease of BDNF expression in the prefrontal cortex six hours after the FST. Regarding neurotransmitters, only accumbal dopamine turnover and hippocampal glutamate content showed an effect of individual differences (i.e. animals with low and high immobility), whereas nearly all parameters showed significant differences across time points. Correlational analyses suggest that immobility in the FST, probably reflecting despair, is related to prefrontal cortical BDNF and to the kinetics observed in several other neurochemical parameters. Taken together, our results suggest that individual differences observed in depression-like behavior can be associated not only with changes in the concentrations of key neurochemical factors but also with differential time courses of such factors.
    Physiology & Behavior 04/2014; 128. DOI:10.1016/j.physbeh.2014.01.037 · 2.98 Impact Factor
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