nervous system
• dendritic spine density is significantly decreased in the caudate putamen, nucleus accumbens and central nucleus of the amygdala, as well as in the hippocampus CA1 region
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• mice show increased G protein coupling for delta opioid receptor (DOR) and mu opioid, but not other Gi/o coupled receptors, in striatal membranes
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behavior/neurological
• mice exhibit impaired striatal-dependent behaviors (hyperactivity, stereotypies, motor impairment in rotarod) and enhanced hippocampus-dependent behaviors (Y-maze, novel object recognition, dual solution cross-maze)
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• mice exhibit impaired motor skill learning in the accelerating rotarod test and fail to improve over trials and sessions
• chronic blockade of delta opioid receptor activity via naltrindole administration transiently (session 2) restores the motor skill learning deficit
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• mice exhibit increased forward locomotion in a novel environment (open field) and this hyperactivity fails to habituate over sessions
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• mice exhibit hyperactive exploratory behavior when exposed to a novel environment
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• mice enter more often into arms of the Y-maze during a 5-min exploration session, show a trend toward higher spontaneous alternation and return significantly less into the same arm, indicating less perseverative errors, while alternate arms returns remain unchanged
• mice visit the objects more often and spend more time exploring the moved object during phase 2 (place phase) in the novel object recognition test
• mice acquire earlier and better a dual-solution cross-maze task using distal extra-maze cues, shift sooner to a response strategy to solve the task (probe trial 1), and reacquire more rapidly this task after spatial reversal than wild-type controls by shifting sooner to an allocentric strategy (probe trial 2)
• chronic naltrindole treatment increases significantly the number of same arm returns in the Y-maze test
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• mice exhibit less perseverative arm reentries in the Y-maze test, indicating enhanced hippocampus-dependent working memory
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• in the elevated plus maze (EPM) test, mice travel a longer distance in the open arms and spend more time in the distal parts, with more frequent flat back approaches, stretched attend postures and head dips than wild-type controls; also, duration of individual head dips is longer than in wild-type controls
• in the anxiety-induced marble-burying test, mice bury less marbles than wild-type controls
• in the novelty suppressed feeding (NSF) test, mice require less time to start feeding in the center of the arena and consume more chow upon return to their home cage than wild-type controls, suggesting reduced conflict anxiety
• chronic naltrindole treatment fails to modify exploration ratios in EPM test but reduced the total number of flat back approaches and stretched attend postures, as well as the number of distal flat back approaches, stretched attend postures, and head dips to control levels
• in the NSF test, chronic naltrindole treatment increases the latency to feed to control levels with no effect on food intake
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• mice exhibit decreased grooming relative to wild-type controls
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• mice exhibit impaired motor coordination and skill learning in the accelerating rotarod test
• however, forelimb motor coordination (string task) and muscular strength (grip test) are normal
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• mice exhibit decreased numbers of rearing relative to wild-type controls
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• mice show non-habituating hyperactivity in a novel environment and increased activity in the Y-maze and novel object recognition tests
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• mice exhibit fewer burying episodes but longer duration of burying episodes than wild-type controls in the marble burying test
• mice show a higher frequency of circling than wild-type controls
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• male, but not female, mice display impaired ability to build a nest
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homeostasis/metabolism
• decreased dopamine levels in the dorsal striatum (caudate putamen) and in the central nucleus of the amygdala but not in the ventral striatum (nucleus accumbens)
• dopamine levels remain normal in other brain regions (prefrontal cortex, dorsal hippocampus, and ventral hippocampus)
• dopamine metabolite 3,4-dihydroxyphenylacetic acid is normal
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• increased dopamine content in the midbrain (ventral tegmental area/substantia nigra pars compacta)
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• increased levels of serotonin (5HT) and its metabolite 5-hydroxyindoleacetic acid (5HIAA) in the dorsal raphe nucleus but no changes in other brain structures
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