Switching between chewing-gum and no-gum at learning and retrieval does not accentuate error production in free recall

Three experiments compared chewing gum to a no gum condition to examine further the finding (Anderson, Berry, Morse & Diotte, 2005) that switching flavour between learning and recall encourages error production independently of free recall. In order to encourage error production, participants in Experiment 1 were told to guess responses at recall, participants in Experiment 2 were required to recall categorised word lists and in Experiment 3 participants repeated the same learning-recall combination on four immediately successive occasions and were required to recall different categorised word lists on each. The experiments produced universally null effects. Consistent with previous research, for correct recall, there were no independent effects of chewing gum for learning or recall and nor was their evidence of context dependency. Error production was not biased towards the inconsistent learning-recall contexts even when participants switched successively between the learning-recall contexts. Finally, there was no evidence that extended temporal exposure to chewing gum was an important determinant of context-dependent memory effects

Cognitive function and mood at high altitude following acclimatization and use of supplemental oxygen and adaptive servoventilation sleep treatments.

Impairments in cognitive function, mood, and sleep quality occur following ascent to high altitude. Low oxygen (hypoxia) and poor sleep quality are both linked to impaired cognitive performance, but their independent contributions at high altitude remain unknown. Adaptive servoventilation (ASV) improves sleep quality by stabilizing breathing and preventing central apneas without supplemental oxygen. We compared the efficacy of ASV and supplemental oxygen sleep treatments for improving daytime cognitive function and mood in high-altitude visitors (N = 18) during acclimatization to 3,800 m. Each night, subjects were randomly provided with ASV, supplemental oxygen (SpO2 > 95%), or no treatment. Each morning subjects completed a series of cognitive function tests and questionnaires to assess mood and multiple aspects of cognitive performance. We found that both ASV and supplemental oxygen (O2) improved daytime feelings of confusion (ASV: p < 0.01; O2: p < 0.05) and fatigue (ASV: p < 0.01; O2: p < 0.01) but did not improve other measures of cognitive performance at high altitude. However, performance improved on the trail making tests (TMT) A and B (p < 0.001), the balloon analog risk test (p < 0.0001), and the psychomotor vigilance test (p < 0.01) over the course of three days at altitude after controlling for effects of sleep treatments. Compared to sea level, subjects reported higher levels of confusion (p < 0.01) and performed worse on the TMT A (p < 0.05) and the emotion recognition test (p < 0.05) on nights when they received no treatment at high altitude. These results suggest that stabilizing breathing (ASV) or increasing oxygenation (supplemental oxygen) during sleep can reduce feelings of fatigue and confusion, but that daytime hypoxia may play a larger role in other cognitive impairments reported at high altitude. Furthermore, this study provides evidence that some aspects of cognition (executive control, risk inhibition, sustained attention) improve with acclimatization

Adolescent D-amphetamine treatment in a rodent model of ADHD: pro-cognitive effects during adolescence and cocaine abuse risk during adulthood

Attention-deficit/hyperactivity disorder (ADHD) is comorbid with cocaine abuse. Whereas initiating ADHD medication in childhood does not alter later cocaine abuse risk, initiating medication during adolescence may increase risk. Preclinical work in the Spontaneously Hypertensive Rat (SHR) model of ADHD found that adolescent methylphenidate increased cocaine self-administration in adulthood, suggesting a need to identify alternatively efficacious medications for teens with ADHD. We examined effects of adolescent d-amphetamine treatment on strategy set shifting performance during adolescence and on cocaine self-administration and reinstatement of cocaine-seeking behavior (cue reactivity) during adulthood in male SHR, Wistar- Kyoto (inbred control), and Wistar (outbred control) rats. During the set shift phase, adolescent SHR needed more trials and had a longer latency to reach criterion, made more regressive errors and trial omissions, and exhibited slower and more variable lever press reaction times. d- Amphetamine improved performance only in SHR by increasing choice accuracy and decreasing errors and latency to criterion. In adulthood, SHR self-administered more cocaine, made more cocaine-seeking responses, and took longer to extinguish lever responding than control strains. Adolescent d-amphetamine did not alter cocaine self-administration in adult rats of any strain, but reduced cocaine seeking during the first of seven reinstatement test sessions in adult SHR. These findings highlight utility of SHR in modeling cognitive dysfunction and comorbid cocaine abuse in ADHD. Unlike methylphenidate, d-amphetamine improved several aspects of flexible learning in adolescent SHR and did not increase cocaine intake or cue reactivity in adult SHR. Thus, adolescent d-amphetamine was superior to methylphenidate in this ADHD model

Adolescent D-amphetamine treatment in a rodent model of ADHD: pro-cognitive effects in adolescence without an impact on cocaine cue reactivity in adulthood

Attention-deficit/hyperactivity disorder (ADHD) is comorbid with cocaine abuse. Whereas initiating ADHD medication in childhood does not alter later cocaine abuse risk, initiating medication during adolescence may increase risk. Preclinical work in the Spontaneously Hypertensive Rat (SHR) model of ADHD found that adolescent methylphenidate increased cocaine self-administration in adulthood, suggesting a need to identify alternatively efficacious medications for teens with ADHD. We examined effects of adolescent d-amphetamine treatment on strategy set shifting performance during adolescence and on cocaine self-administration and reinstatement of cocaine-seeking behavior (cue reactivity) during adulthood in male SHR, Wistar-Kyoto (inbred control), and Wistar (outbred control) rats. During the set shift phase, adolescent SHR needed more trials and had a longer latency to reach criterion, made more regressive errors and trial omissions, and exhibited slower and more variable lever press reaction times. d-Amphetamine improved performance only in SHR by increasing choice accuracy and decreasing errors and latency to criterion. In adulthood, SHR self-administered more cocaine, made more cocaine-seeking responses, and took longer to extinguish lever responding than control strains. Adolescent d-amphetamine did not alter cocaine self-administration in adult rats of any strain, but reduced cocaine seeking during the first of seven reinstatement test sessions in adult SHR. These findings highlight utility of SHR in modeling cognitive dysfunction and comorbid cocaine abuse in ADHD. Unlike methylphenidate, d-amphetamine improved several aspects of flexible learning in adolescent SHR and did not increase cocaine intake or cue reactivity in adult SHR. Thus, adolescent d-amphetamine was superior to methylphenidate in this ADHD model.R01 DA011716 - NIDA NIH HHS; DA011716 - NIDA NIH HH

Enhancement of psychosocial treatment with D-cycloserine: models, moderators, and future directions

Advances in the understanding of the neurobiology of fear extinction have resulted in the development of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure treatment. We review a decade of research that has focused on the efficacy of DCS for augmenting the mechanisms (e.g., fear extinction) and outcome of exposure treatment across the anxiety disorders. Following a series of small-scale studies offering strong support for this clinical application, more recent larger-scale studies have yielded mixed results, with some showing weak or no effects. We discuss possible explanations for the mixed findings, pointing to both patient and session (i.e., learning experiences) characteristics as possible moderators of efficacy, and offer directions for future research in this area. We also review recent studies that have aimed to extend the work on DCS augmentation of exposure therapy for the anxiety disorders to DCS enhancement of learning-based interventions for addiction, anorexia nervosa, schizophrenia, and depression. Here, we attend to both DCS effects on facilitating therapeutic outcomes and additional therapeutic mechanisms beyond fear extinction (e.g., appetitive extinction, hippocampal-dependent learning).F31 MH103969 - NIMH NIH HHS; K24 DA030443 - NIDA NIH HHS; R34 MH099309 - NIMH NIH HHS; R34 MH086668 - NIMH NIH HHS; R21 MH102646 - NIMH NIH HHS; R34 MH099318 - NIMH NIH HH

Pavlovian Conditioning Between Cocaine Stimulant Effects and a Discrete Sensory Cue: Implementation of an Alternating Conditioning Procedure

Cocaine addiction is associated with an extremely high rate of relapse, the resumption of drug taking behavior following a period of abstinence. Relapse may be induced by exposure to drug-associated cues, stress, or drug challenge. Rodent models of addiction investigate reinstatement, the resumption of drug-seeking behavior following a period of abstinence. This study investigated the necessary procedures for establishing Pavlovian conditioning between a discrete sensory cue and cocaine stimulant effects (15.0 mg/kg, IP). Successful conditioning was indicated by cue induced conditioned hyperactivity. In Experiment 1, a simple discrete visual cue failed to be attributed salience. Cocaine-treated rats showed heightened locomotor activity independent of cue condition, suggestive of contextual conditioning. Experiment 2 replaced the simple visual cue with a compound auditory/visual cue and implemented various procedural adaptations to prevent contextual conditioning; comparable results were observed. Experiment 3 introduced an alternating cue conditioning/no cue conditioning training regimen with 6 drug-cue pairings over 12 days. This alternating training procedure minimized contextual conditioning and resulted in successful attribution of salience to the discrete cue for tests after 3, 14, and 28 days of withdrawal. This study suggests that an alternating drug-cue pairing training procedure can be used to establish conditioned locomotor activity specific to a discrete compound sensory cue in Sprague-Dawley rats

Pavlovian Conditioning Between Cocaine Stimulant Effects and a Discrete Sensory Cue: Implementation of an Alternating Conditioning Procedure

Cocaine addiction is associated with an extremely high rate of relapse, the resumption of drug taking behavior following a period of abstinence. Relapse may be induced by exposure to drug-associated cues, stress, or drug challenge. Rodent models of addiction investigate reinstatement, the resumption of drug-seeking behavior following a period of abstinence. This study investigated the necessary procedures for establishing Pavlovian conditioning between a discrete sensory cue and cocaine stimulant effects (15.0 mg/kg, IP). Successful conditioning was indicated by cue induced conditioned hyperactivity. In Experiment 1, a simple discrete visual cue failed to be attributed salience. Cocaine-treated rats showed heightened locomotor activity independent of cue condition, suggestive of contextual conditioning. Experiment 2 replaced the simple visual cue with a compound auditory/visual cue and implemented various procedural adaptations to prevent contextual conditioning; comparable results were observed. Experiment 3 introduced an alternating cue conditioning/no cue conditioning training regimen with 6 drug-cue pairings over 12 days. This alternating training procedure minimized contextual conditioning and resulted in successful attribution of salience to the discrete cue for tests after 3, 14, and 28 days of withdrawal. This study suggests that an alternating drug-cue pairing training procedure can be used to establish conditioned locomotor activity specific to a discrete compound sensory cue in Sprague-Dawley rats

Chronic Alcohol Exposure Alters Behavioral and Synaptic Plasticity of the Rodent Prefrontal Cortex

In the present study, we used a mouse model of chronic intermittent ethanol (CIE) exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC). In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of excitatory post-synaptic currents (EPSCs) in mPFC layer V pyramidal neurons revealed that CIE exposure resulted in an increase in the NMDA/AMPA current ratio. This increase appeared to result from a selective increase in the NMDA component of the EPSC. Consistent with this, Western blot analysis of the postsynaptic density fraction showed that while there was no change in expression of the AMPA GluR1 subunit, NMDA NR1 and NRB subunits were significantly increased in CIE exposed mice when examined immediately after the last episode of alcohol exposure. Unexpectedly, this increase in NR1 and NR2B was no longer observed after 1-week of withdrawal in spite of a persistent increase in synaptic NMDA currents. Analysis of spines on the basal dendrites of layer V neurons revealed that while the total density of spines was not altered, there was a selective increase in the density of mushroom-type spines following CIE exposure. Examination of NMDA-receptor mediated spike-timing-dependent plasticity (STDP) showed that CIE exposure was associated with altered expression of long-term potentiation (LTP). Lastly, behavioral studies using an attentional set-shifting task that depends upon the mPFC for optimal performance revealed deficits in cognitive flexibility in CIE exposed mice when tested up to 1-week after the last episode of alcohol exposure. Taken together, these observations are consistent with those in human alcoholics showing protracted deficits in executive function, and suggest these deficits may be associated with alterations in synaptic plasticity in the mPFC