Enhanced learning by posttrial injection of H1-but not H2-histaminergic antagonists into the nucleus basalis magnocellularis region

The aim of this study was to examine the effects of histaminergic antagonists on memory upon injection into the region of the nucleus basalis magnocellularis (NBM). In experiment 1, rats with chronically implanted cannulae were trained on the uphill avoidance task, which involves a punishment of a high-probability turning response on a tilted platform (negative geotaxis). Immediately after the training trial, that is, after a tail shock was administered upon performing the response, rats received one microinjection (0.5 microliter) of H1-receptor blocker chlorpheniramine (dose range 0.1 to 20 microgram) or the H2-receptor blocker ranitidine (same dose range) or saline into the NBM region. When tested 24 h later, rats treated with chlorpheniramine (20 micrograms) had significantly longer uphill latencies than vehicle controls and ranitidine-treated animals, indicative of superior learning of the avoidance response. In experiment 2, a test for possible proactive effects of posttrial chlorpheniramine on performance during the retention trial was performed. Animals were injected with either 20 micrograms chlorpheniramine or saline immediately after the training trial of the uphill task. One chlorpheniramine control group was treated with a delay of 5 h. Additional groups which received chlorpheniramine or vehicle after the training trial but no trail shock were included. When tested 24 h later, rats injected with 20 micrograms chlorpheniramine again exhibited significantly longer uphill latencies than did vehicle-injected rats. Retention latencies for the rats of the chlorpheniramine 5-h delayed group did not differ from those of the vehicle-injected rats, ruling out proactive effects of chlorpheniramine on performance. In summary, the histaminergic H1-blocker chlorpheniramine can enhance mnemonic functioning in addition to its reinforcing effects upon NBM injection as reported previously.     

趋近和回避动机的区分及其对心理病理学的影响

趋近和回避是动机的两种最基本形式, 反映着个体与环境的相互作用方式, 是个体适应环境的核心机能。回避动机保证了个体的生存, 趋近动机则促进个体的成长。两类动机系统在前额叶皮层呈不对称偏侧化分布, 趋近动机与左侧额叶皮层激活相连, 回避动机与右侧额叶皮层激活相连。Youngstorm 和Izard等认为两类动机系统失调可能与一系列的情绪和行为问题有关, 如躁狂、抑郁、焦虑和儿童多动症等。这一观点已得到一些相关研究和临床研究证实。建议未来研究关注趋近-回避动机区分与情绪和认知功能研究的融合, 进一步检验趋近-回避动机系统失调模型, 并加强趋近和回避动机系统的可塑性研究。     

Ethanol state-dependent memory: involvement of dorsal hippocampal muscarinic and nicotinic receptors

In the present study, the effects of bilateral injections of cholinergic agents into the hippocampal CA1 regions (intra-CA1) on ethanol state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Pre-training intraperitoneal injection (i.p.) of ethanol (0.25, 0.5 and 1 g/kg) dose dependently induced impairment of memory retention. Pre-test administration of ethanol (0.5 and 1 g/kg, i.p.) induced state-dependent retrieval of the memory acquired under pre-training ethanol (1 g/kg, i.p.) influence. Pre-test intra-CA1 injection of physostigmine (2.5 and 5 μg/mouse, intra-CA1) or nicotine (0.3 and 0.5 μg/mouse, intra-CA1) improved pre-training ethanol (1 g/kg)-induced retrieval impairment. Moreover, pre-test administration of physostigmine (2.5 and 5 μg/mouse, intra-CA1) or nicotine (0.3 and 0.5 μg/mouse, intra-CA1) with an ineffective dose of ethanol (0.25 g/kg) significantly restored the retrieval and induced ethanol state-dependent memory. Pre-test intra-CA1 injection of the muscarinic receptor antagonist, atropine (4 and 8 μg/mouse, intra-CA1) or the nicotinic receptor antagonist, mecamylamine (2 and 4 μg/mouse, intra-CA1) 5 min before the administration of ethanol (1 g/kg, i.p.) dose dependently inhibited ethanol state-dependent memory. Pre-test intra-CA1 administration of physostigmine (0.5, 2.5 and 5 μg/mouse), atropine (2, 4 and 8 μg/mouse), nicotine (0.1, 0.3 and 0.5 μg/mouse) or mecamylamine (1, 2 and 4 μg/mouse) alone cannot affect memory retention. These findings implicate the involvement of a dorsal hippocampal cholinergic mechanism in ethanol state-dependent memory and also it can be concluded that there may be a cross-state dependency between ethanol and acetylcholine.     

Rigidity in social and emotional memory in the R6/2 mouse model of Huntington's disease

Four experiments were conducted to examine social and emotional memory in the R6/2 transgenic mouse model of Huntington’s disease. First, R6/2 mice were tested in a social transmission of food preference task where they had to acquire a preference for a flavoured food (acquisition) and subsequently to learn a preference for a different flavour (shifted reinforcement). R6/2 mice performed well in the acquisition trial. However, they were impaired in the shifted reinforcement trial and perseverated on the first preference learned. Second, mice were trained in an inhibitory avoidance paradigm, with either one or two footshocks delivered during the training. WT mice given one footshock showed retention levels lower than those of mice trained with two footshocks. By contrast, there was no difference in retention levels of R6/2 mice given either one or two footshocks. Third, mice were tested in an active avoidance task that paired a mild footshock with a warning light. R6/2 mice had a strong age-dependent deficit in this task. Finally, mice were tested in a conditioned taste aversion task that paired a saccharine solution with a nausea-inducing agent (LiCl). R6/2 mice displayed normal aversion, however this was not extinguished following repeated exposure to saccharine solution alone. Our data show that while R6/2 mice have functional hippocampus-based memory, they have deficits in striatum-based memory skills. Further, social and emotional memories appear to be encoded in a rigid way that is not influenced by subsequent learning or by arousal levels.     

Upregulation of hippocampal TrkB and synaptotagmin is involved in treadmill exercise-enhanced aversive memory in mice

Cognitive functions usually involve various synaptic proteins and neurotrophic factors in the hippocampus. However, whether treadmill exercise can improve learning and memory by upregulating some of these molecules remain unraveled. To address this question, male BALB/c mice were divided into control and exercise groups, the latter group went through 4 weeks of treadmill exercise training. At the end of exercise training period, they were either tested for passive avoidance (PA) performance or sacrificed for quantifying the hippocampal levels of brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB, the BDNF receptor), synaptotagmin (a Ca²⁺-dependent synaptic vesicle protein), and SNAP-25 (a presynaptic vesicular fusion protein). Our results showed that treadmill exercise training (1) increased the retention latency without affecting the fear acquisition in the PA test, (2) transiently increased the hippocampal BDNF level at 1, 2, and 4 h after the completion of exercise training, and (3) persistently increased the hippocampal protein levels of full-length TrkB, phosphorylated TrkB and synaptotagmin, but not truncated TrkB or SNAP-25. Moreover, the protein expression level of full-length TrkB or synaptotagmin was positively correlated with PA performance in mice. Finally, inhibition of TrkB signaling by K252a abolished the exercise-facilitated PA performance and upregulation of TrkB and synaptotagmin. Taken together, these data suggest that the upregulation of TrkB and synaptotagmin in the hippocampus contributes to the exercise-facilitated aversive memory.     

Avoidance of timeout from response-independent food: effects of delivery rate and quality

In three experiments, a rat's lever presses could postpone timeouts from food pellets delivered on response-independent schedules. In Experiment 1, the pellets were delivered at variable-time (VT) rates ranging from VT 0.5 to VT 8 min. Experiment 2 replicated the VT 1 min and VT 8 min conditions of Experiment 1 with new subjects. Finally, subjects in Experiment 3 could postpone timeouts from delivery of pellets that differed in quality rather than quantity (unsweetened versus sweetened pellets). In general, response rates and success in avoiding increased as a function of the rate and quality of the pellets. Also, performance efficiency increased as the experiments progressed, that is, the avoidance response occurred later and later in the response-timeout interval. The results support the conclusion that timeout from reinforcement has functional properties similar to those of more commonly studied aversive stimuli (e.g., shock).     

Electrical stimulation of the pedunculopontine tegmental nucleus in freely moving awake rats: time- and site-specific effects on two-way active avoidance conditioning

The pedunculopontine tegmental nucleus (PPTg) is involved in the regulation of thalamocortical transmission and of several functions related to ventral and dorsal striatal circuits. Stimulation of the PPTg in anesthetized animals increases cortical arousal, cortical acetylcholine release, bursting activity of mesopontine dopaminergic cells, and striatal dopamine release. It was hypothetized that PPTg stimulation could improve learning by enhancing cortical arousal and optimizing the activity of striatal circuits. We tested whether electrical stimulation (ES) of the PPTg, applied to freely-moving awake rats previously implanted with a chronic electrode, would improve the acquisition and/or the retention of two-way active avoidance conditioning, and whether this effect would depend on the specific PPTg region stimulated (anterior vs posterior) and on the time of ES: just before (pre-training) or after (post-training) each of three training sessions. The treatment consisted of 20 min of ES (0.2 ms pulses at 100 Hz; current intensity: 40-80 microA). The results showed that (1) this stimulation did not induce either any signs of distress nor abnormal behaviors, apart from some motor stereotyped behaviors that disappeared when current intensity was lowered; (2) pre-training ES applied to the anterior PPTg improved the acquisition of two-way active avoidance, (3) no learning improvement was found after either post-training ES of the anterior PPTg, or pre- and post-training ES of the posterior PPTg. The results give support to a role of PPTg in learning-related processes, and point to the existence of functional PPTg regions.     

The impact of experiential avoidance on the reduction of depression in treatment for borderline personality disorder

Background

Reducing symptoms of depression is an important target in the treatment of borderline personality disorder (BPD). Although current treatments for BPD are effective in reducing depression, the average post-treatment level of depression remains high.

Aim

To test whether experiential avoidance (EA) impedes the reduction of depression during treatment for BPD.

Method

EA and depression were assessed in 81 clients at baseline and 4-month intervals during 1 year of therapy. Simple correlations, hierarchical linear modeling, and latent difference score models were used to investigate the association between self-reports of EA and both self-reports and observer-based ratings of depression.

Results

EA was positively associated with greater severity of depression at all points of assessment, and changes in EA were positively associated with changes in depression. Moreover, EA significantly predicted less subsequent reduction in depression whereas no such effect was found for depression on subsequent EA.

Conclusion

The findings are consistent with the hypothesis that EA impedes the reduction of depression in the treatment of BPD and should thus be considered an important treatment target.     

Unconstraining theories of embodied cognition

The approach/avoidance effect refers to the finding that valenced stimuli trigger approach and avoidance actions. Markman and Brendl [Markman, A. B., & Brendl, M. (2005). Constraining theories of embodied cognition. Psychological Science, 16, 6-16] argued that this effect is not a truly embodied phenomenon, but depends on participants’ symbolic representation of the self.In their study, participants moved valenced words toward or away from their own name on the computer screen. This would induce participants to form a ‘disembodied’ self-representation at the location of their name, outside of the body. Approach/avoidance effects occurred with respect to the participant’s name, rather than with respect to the body.In three experiments, we demonstrate that similar effects are found when the name is replaced by a positive word, a negative word or even when no word is presented at all. This suggests that the ‘disembodied self’ explanation of Markman and Brendl is incorrect, and that their findings do not necessarily constrain embodied theories of cognition.     

Inhibitory response capacities of bilateral lower and upper extremities in children with developmental coordination disorder in endogenous and exogenous orienting modes

This study was designed to investigate separately the inhibitory response capacity and the lateralization effect in children with developmental coordination disorder (DCD) in the endogenous and exogenous modes of orienting attention. Children with DCD on the lower extremities (DCD-LEs), along with age-matched controls, completed four tasks that involved various applications of asynchronous stimuli to the feet or hands at various intervals. The results demonstrated that children with DCD-LEs had a significantly longer reaction time than the controls for all tasks, and were not alert to the appearance of the target. However, they displayed a deficit in volitional shifts of attention (endogenous mode), but not in automatic dislocation of attention (exogenous mode), whenever they performed the tasks with either their lower or their upper-limbs-even 6 months after the initial study. These findings confirm the deficit in the inhibitory response capacity in terms of volitional movement of attention by children with DCD. Additionally, the negative effect of lateralization on the bilateral extremities was not present in children with DCD-LEs. Significantly differences in response ability were detected only between the dominant and non-dominant sides of upper-limbs, but not between the lower-limbs, suggesting a future avenue for further experimentation on bilateral extremities.