People who have a high """"""""drive"""""""" for novel and arousing sensory stimulation (i.e., high sensation-seekers) are known to use drugs more frequently than low sensation-seekers. One interpretation of this relationship is that high sensation-seekers are predisposed biologically to find both novel stimuli and drugs to be more rewarding than low sensation-seekers. The present research will determine if novelty activates the mesolimbic DA system in a manner analogous to amphetamine, and will examine the potential neurochemical connection between novelty- and drug-seeking behaviors. Specifically, the role of D1 and D2 DA receptors in novelty-seeking will be evaluated in rats. Other experiments will be conducted to explore the possibility that reactivity to stress may influence novelty preference behavior. In separate experiments, rats will be categorized as either """"""""high"""""""" or """"""""low"""""""" in novelty preference behavior based upon their approach towards a novel environmental stimulus. These animals will then be tested for their sensitivity to the locomotor-activating and rewarding effects of amphetamine using the conditioned place preference paradigm. In addition to amphetamine, another psychostimulant (cocaine), as well as other drug classes (diazepam and morphine), will be evaluated in order to assess the generality of the findings. A parallel set of neurochemical experiments will assess whether any behavioral differences reflect a change in the functional activity of the mesolimbic DA system. In another set of experiments, rats will be raised from 21 days of age in isolation cages (1 per cage), group cages (3 per cage) or in an enriched environment with novel toys (12 per cage). At 50-60 days of age, the animals will be tested for their preference for a novel environment, as well as their behavioral reactivity to amphetamine and other drugs of abuse. In addition, isolated-, grouped- and enriched-reared rats will be examined neurochemically to determine the functional activity of the mesolimbic DA system when challenged with novel stimuli or drugs of abuse.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
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Drug Abuse Biomedical Research Review Committee (DABR)
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University of Kentucky
Schools of Arts and Sciences
United States
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Bardo, M T (1998) Neuropharmacological mechanisms of drug reward: beyond dopamine in the nucleus accumbens. Crit Rev Neurobiol 12:37-67
Bardo, M T; Robinet, P M; Hammer Jr, R F (1997) Effect of differential rearing environments on morphine-induced behaviors, opioid receptors and dopamine synthesis. Neuropharmacology 36:251-9
Bevins, R A; Klebaur, J E; Bardo, M T (1997) Individual differences in response to novelty, amphetamine-induced activity and drug discrimination in rats. Behav Pharmacol 8:113-23
Bevins, R A; Klebaur, J E; Bardo, M T (1997) 7-OH-DPAT has d-amphetamine-like discriminative stimulus properties. Pharmacol Biochem Behav 58:485-90
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Bardo, M T; Rowlett, J K; Harris, M J (1995) Conditioned place preference using opiate and stimulant drugs: a meta-analysis. Neurosci Biobehav Rev 19:39-51
Bowling, S L; Bardo, M T (1994) Locomotor and rewarding effects of amphetamine in enriched, social, and isolate reared rats. Pharmacol Biochem Behav 48:459-64
Bowling, S L; Rowlett, J K; Bardo, M T (1993) The effect of environmental enrichment on amphetamine-stimulated locomotor activity, dopamine synthesis and dopamine release. Neuropharmacology 32:885-93