Marinelli M. The many facets of the locomotor response to a novel environment test: theoretical comment on Mitchell, Cunningham, and Mark (2005). Behav Neurosci 119: 1144-1151

Department of Cellular & Molecular Pharmacology, Rosalind Franklin University of Medicine and Science/The Chicago Medical School, North Chicago, IL 60064, USA.
Behavioral Neuroscience (Impact Factor: 2.73). 09/2005; 119(4):1144-51. DOI: 10.1037/0735-7044.119.4.1144
Source: PubMed


Several animal studies have shown that there is a positive correlation between locomotor activity in response to a novel environment and acquisition of drug self-administration behavior. This finding led to the assumption that animals with heightened reactivity to novel environments are more sensitive to the rewarding effects of drugs compared with animals with reduced reactivity. But are these individuals really more responsive to drugs, or could they have enhanced sensitivity to rewards in general or even simply be better learners? In the previous issue of this journal, J. M. Mitchell, C. L. Cunningham, and G. P. Mark (2005), investigated these important matters. They reported that the locomotor response to a novel environment does not predict responding for cocaine but reflects overall differences in the ability to learn operant tasks. ((c) 2005 APA, all rights reserved).

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    • "In fact, in outbred rodent populations there is a normal distribution of this trait. However, we and others (see Marinelli, 2005) have noted significant batch-to-batch variation in the HR and LR traits in outbred populations and it has been difficult to determine whether or not the " sensation-seeking " trait is stable or state dependent in these populations. Thus, if we were to discover the genetic and neural causes that lead to vulnerability to drug-seeking behavior, it was important to identify the antecedent variables that determine these traits. "
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    ABSTRACT: Human genetic and epidemiological studies provide evidence that only a subset of individuals who experiment with potentially addictive drugs become addicts. What renders some individuals susceptible to addiction remains to be determined, but most would agree that there is no single trait underlying the disorder. However, there is evidence in humans that addiction liability has a genetic component, and that certain personality characteristics related to temperament (e.g. the sensation-seeking trait) are associated with individual differences in addiction liability. Consequently, we have used a selective breeding strategy based on locomotor response to a novel environment to generate two lines of rats with distinct behavioral characteristics. We have found that the resulting phenotypes differ on a number of neurobehavioral dimensions relevant to addiction. Relative to bred low-responder (bLR) rats, bred high-responder (bHR) rats exhibit increased exploratory behavior, are more impulsive, more aggressive, seek stimuli associated with rewards, and show a greater tendency to relapse. We therefore utilize this unique animal model to parse the genetic, neural and environmental factors that contribute to addiction liability. Our work shows that the glucocorticoid receptor (GR), dopaminergic molecules, and members of the fibroblast growth factor family are among the neurotransmitters and neuromodulators that play a role in both the initial susceptibility to addiction as well as the altered neural responses that follow chronic drug exposure. Moreover, our findings suggest that the hippocampus plays a major role in mediating vulnerability to addiction. It is hoped that this work will emphasize the importance of personalized treatment strategies and identify novel therapeutic targets for humans suffering from addictive disorders.
    Neuropharmacology 04/2013; 76. DOI:10.1016/j.neuropharm.2013.04.033 · 5.11 Impact Factor
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    • "Similarly, we observed that exploration of a novel open field, but not of a novel object in the home cage was related to cocaine selfadministration . The locomotor response to novelty has been reported to not predict " addiction-like " behaviors (Belin et al. 2008), and may be related to general activity and ability to learn an operant response (Mitchell et al. 2005) but see (Marinelli 2005). "
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    ABSTRACT: Early-onset drug taking is associated with increased likelihood of addiction, but it is unclear whether early onset is causal in development of addiction. Many other factors are associated with increased risk of addiction and also promote early intake. Here, a rodent model is used to explore the causality of early onset in development of self-administration and addiction-like behavior and to examine factors that promote self-administration. We used cocaine self-administration to examine drug taking and addiction-like behavior in adolescent and adult rats a priori characterized for their locomotor responses to novelty and cocaine and behavior in the light-dark task. Adolescent animals initially sought more cocaine than adults. However, as the adolescents matured, their intake fell and they did not differ from adults in terms of unreinforced lever-pressing, extinction or reinstatement behavior. For both age groups, self-administration was positively correlated with the locomotor response to novelty, the locomotor response to cocaine, and with time in light in the light-dark task. The rats that were insensitive to cocaine's locomotor effects and that spent the least time in light in the light-dark task sought the least cocaine, appearing to be "protected" from the reinforcing effects of cocaine. There was no difference between the two age groups in appearance of this "protected" phenotype. These results suggest that early onset of drug taking may promote increased use, but does not promote progression to addiction-like behavior. Furthermore, protective factors, such as innate anxiety and insensitivity to cocaine's pharmacological effects, function across developmental stages.
    Psychopharmacology 02/2011; 215(3):493-504. DOI:10.1007/s00213-011-2216-5 · 3.88 Impact Factor
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    • "In addition, such individual differences in drug reactivity can be studied experimentally, in rodent lines that have been selectively bred for drug preference, or in animals that show a high locomotor response to a novel environment. Thus, high responders to novelty (HRs) are known to exhibit greater responding to psychostimulant drugs than low responders (LRs) (for review, see Marinelli, 2005) and greater ethanol intake in certain conditions (Cools and Gingras, 1998). In this model of enhanced addiction liability, the firing rate of dopamine cells, measured with in vivo extracellular recordings in anesthetized rats, was shown to be elevated in HR vs. LR rats (Marinelli and White, 2000). "
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    ABSTRACT: There has been a great deal of activity in recent years in the study of the direct effects of ethanol on the dopamine reward system originating in the ventral tegmental area (VTA). In addition, recent evidence suggests that acetaldehyde formed from ethanol in the brain or periphery may be a crucial factor in the central effects of ethanol. This critical review examines the actions of ethanol and acetaldehyde on neurons of the VTA and the possible interactions with stress, with a focus on electrophysiological studies in vivo and in vitro. Ethanol has specific effects on dopamine neurons and there is recent evidence that some of the in vivo and in vitro effects of ethanol are mediated by acetaldehyde. Stress has some analogous actions on neuronal activity in the VTA, and the interactions between the effects of stress and alcohol on VTA neurons may be a factor in ethanol-seeking behavior. Taken together, the evidence suggests that stress may contribute to the activating effects of ethanol on dopamine VTA neurons, that at least some actions of ethanol on dopamine VTA neurons are mediated by acetaldehyde, and that the interaction between stress and alcohol could play a role in susceptibility to alcoholism. The link between acetaldehyde and ethanol actions on brain reward pathways may provide a new avenue for the development of agents to reduce alcohol craving.
    Alcohol (Fayetteville, N.Y.) 11/2009; 43(7):531-9. DOI:10.1016/j.alcohol.2009.05.004 · 2.01 Impact Factor
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