Neuroscience
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The development and maintenance of cocaine addiction depend heavily on learned reward-environment associations that can induce drug-seeking behavior and relapse. Understanding the mechanisms underlying these cue-induced conditioned responses is important for relapse prevention. To test whether intracellular responses measured after cocaine conditioned place preference (CPP) expression are context-dependent, we re-exposed cocaine-treated rats (drug-free) to an environment previously paired with cocaine or saline, 24h after the CPP test. ⋯ Conversely, the higher cocaine dose, independent of environment, resulted in increased NAc FosB, ΔFosB and phosphorylated CREB (pCREB) protein levels compared to those conditioned with 5mg/kg cocaine (non-CPP-expressing). Our results suggest that NAc ERK phosphorylation may be involved with retrieving the contextual information of a cocaine-association, without necessarily motivating the expression of CPP behavior. Additionally, we show distinct patterns of intracellular responses in the NAc and CPu indicating a region-specific role for pERK/pCREB/FosB intracellular signaling in the retrieval of cocaine-context associations.
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The present research explored the cortical correlates of emotional memories in response to words and pictures. Subjects' performance (Accuracy Index, AI; response times, RTs; RTs/AI) was considered when a repetitive Transcranial Magnetic Stimulation (rTMS) was applied on the left dorsolateral prefrontal cortex (LDLPFC). Specifically, the role of LDLPFC was tested by performing a memory task, in which old (previously encoded targets) and new (previously not encoded distractors) emotional pictures/words had to be recognized. ⋯ Moreover no significant differences were found between stimulus categories. A direct relationship was also observed between subjective evaluation of emotional cues and memory performance when rTMS was applied to LDLPFC. Supported by valence and approach model of emotions, we supposed that a left lateralized prefrontal system may induce a better recognition of positive high arousal words, and that evaluation of emotional cue is related to prefrontal activation, affecting the recognition memories of emotions.
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The μ opioid receptor (MOR) and κ opioid receptor (KOR) have been implicated in pair-bond formation and maintenance in socially monogamous species. Utilizing monogamous titi monkeys (Callicebus cupreus), the present study examined the potential role opioids play in modulating the response to separation, a potent challenge to the pair-bond. In Experiment 1, paired male titi monkeys were separated from their pair-mate for 30-min and then received saline, naloxone (1.0mg/kg), morphine (0.25mg/kg), or the KOR agonist, U50,488 (0.01, 0.03, or 0.1mg/kg) in a counter-balanced fashion, immediately prior to a 30-min reunion with their mate. ⋯ Blood samples were collected at the time of injection and immediately before and after separation. Administration of the low dose of GNTI decreased the locomotor component of the separation response compared to vehicle. The present study found that the opioid system is involved in both the affiliative and separation distress components of a pair-bond, and these components are regulated by different opioid receptors.
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The present study has been designed to explore the possible interaction between hemeoxygenase-1 (HO-1) and glycogen synthase kinase-3β (GSK-3β) pathway in 3-nitropropionic acid (3-NP)-induced neurotoxicity in rats. 3-NP produces neurotoxicity by inhibition of the mitochondrial complex II (enzyme succinate dehydrogenase) and by sensitizing the N-methyl-D-aspartate receptor. Recent studies have reported the therapeutic potential of HO-1/GSK-3β modulators in different neurodegenerative disorders. However, their exact role is yet to be explored. ⋯ Pretreatment with Tin (IV) protoporphyrin (40 μM/kg), HO-1 inhibitor reversed the beneficial effect of LiCl and hemin. Outcomes of the present study suggest that HO-1 and GSK-3β enzymes are involved in the pathophysiology of HD. The modulators of both the pathways might be used as adjuvants or prophylactic therapy for the treatment of HD-like symptoms.
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Previously, we have demonstrated a role for fibroblast growth factor (Fgf) in spinal cord regeneration in both zebrafish and mouse. We have shown that exogenous Fgf2 treatment attenuates astrocytic gliosis and induces glia cells to become progenitors that undergo neurogenesis as well as differentiating into bipolar astrocytes that support axonal regeneration (Goldshmit et al., 2012, 2014). One of the downstream signaling target genes of Fgf is spry4, which acts as a feedback inhibitor for Fgf signaling. ⋯ We demonstrate that in spry4-/- mice inflammatory responses, such as tumor necrosis factor α (TNFα) secretion and macrophage/neutrophil invasion into the lesion site are reduced. In addition, astrocytic gliosis is attenuated and neuronal survival is increased. These results further support a pro-regenerative role of Fgf after SCI, and suggest that increased endogenous Fgf signaling after SCI may contribute to functional recovery and therefore presents this pathway as a target for new therapy development.