Behavioural brain research
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Cocaine is a potent disruptor of photic and non-photic pathways for circadian entrainment of the master circadian clock of the suprachiasmatic nucleus (SCN). These actions of cocaine likely involve its modulation of molecular (clock gene) components for SCN clock timekeeping. At present, however, the physiological basis of such an interaction is unclear. ⋯ In the light pulse trial, Per2 mutants exhibited larger photic phase-delays than did WTs, and the attenuating action of cocaine on this response was proportionately larger than in WTs. These data indicate that the Per2 clock gene is a potent modulator of cocaine's actions in the circadian system. With regard to non-photic phase-resetting, the SCN is confirmed as a direct target of cocaine action; however, Per2 modulation of this effect likely occurs outside of the SCN.
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Numerous animal model studies in the past decade have demonstrated that pharmacological elevation of cyclic AMP (cAMP) alone, or in combination with other treatments, can promote axonal regeneration after spinal cord injury. Elevation of cAMP via the phosphodiesterase 4 (PDE4) inhibitor, rolipram, decreases neuronal sensitivity to myelin inhibitors, increases growth potential and is neuroprotective. Rolipram's ability to cross the blood-brain barrier makes it a practical and promising treatment for CNS regeneration. ⋯ Stereological analysis revealed no significant differences in lesion volume and length. By contrast, spared white matter was significantly higher in the group treated with rolipram. Our results suggest a therapeutic role for rolipram delivered alone following acute SCI.
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Following early clinical leads, the adenosine A(2A)R receptor (A(2A)R) has continued to attract attention as a potential novel target for treating schizophrenia, especially against the negative and cognitive symptoms of the disease because of A(2A)R's unique modulatory action over glutamatergic in addition to dopaminergic signaling. Through (i) the antagonistic interaction with the dopamine D(2) receptor, and (ii) the regulation of glutamate release and N-methyl-d-aspartate receptor function, striatal A(2A)R is ideally positioned to fine-tune the dopamine-glutamate balance, the disturbance of which is implicated in the pathophysiology of schizophrenia. However, the precise function of striatal A(2A)Rs in the regulation of schizophrenia-relevant behavior is poorly understood. ⋯ We found that neither LI nor PPI was significantly affected in st-A(2A)R-KO mice, although a deficit in active avoidance learning was identified in these animals. The latter phenotype, however, was not replicated in another form of aversive conditioning - namely, conditioned taste aversion. Hence, the present study shows that neither learned inattention (as measured by LI) nor sensory gating (as indexed by PPI) requires the integrity of striatal A(2A)Rs - a finding that may undermine the hypothesized importance of A(2A)R in the genesis and/or treatment of schizophrenia.
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Age-related priming of microglia and release of inflammatory cytokines, such as interleukin-1β (IL-1β) and interleuekin-6 (IL-6) have been associated with deficits in cognitive function. The present study assessed whether treatment with minocycline could improve spatial cognition in aged mice, and whether these improvements in behavior were associated with reduced microglia activation and an enhancement in hippocampal neurogenesis. Adult (3 months) and aged (22 months) male BALB/c mice received minocycline in their drinking water or control mice received distilled water for 20 days. ⋯ Minocycline reduced the average size of Iba-1 positive cells and total Iba-1 counts, but did not affect hippocampal cytokine gene expression. Minocycline increased neurogenesis in adults but not aged mice. Collectively, the data indicate that treatment with minocycline may recover some aspects of cognitive decline associated with aging, but the effect appears to be unrelated to adult hippocampal neurogenesis.
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Many mammals can utilize social information to learn by observation of conspecifics (social learning). Social learning of fear is expected to be especially advantageous for survival. However, disruption of social development in early life can impair social cognition and might also be expected to disrupt social learning. ⋯ These results demonstrate that observational fear conditioning is impaired by social isolation, and provide a model to study impaired social affective learning. Impaired social cognition, manifested as inability to recognize or appropriately interpret social cues, is a symptom of several psychiatric disorders. Better understanding of the mechanisms of impaired social fear learning can lead to novel treatments for social cognition symptoms of psychiatric disorders.