The Role of Time Perspective and Mindfulness on Life Satisfaction in the United States of America, Spain, Poland and Japan: A Cross-Cultural Study.

We assessed the cross-cultural role of Time Perspective (TP) tendencies [Past Positive (PP), Past Negative (PN), Present Hedonistic (PH), Present Fatalistic (PF), and Future (F)], the Deviation from a Balanced Time Perspective (DBTP) profile, the Deviation from a Negative Time Perspective (DNTP) profile, and mindfulness on life satisfaction (LS). The sample consisted of psychology undergraduate students (N= 867, MAGE= 20.19, SD= 3.417) in four countries: USA, Spain, Poland and Japan. We used a 17-item short version of the Zimbardo Time Perspective Inventory (ZTPI), the Mindful Attention Awareness Scale (MAAS), and the Satisfaction with Life Scale (SWLS) in all countries. For ensuring measurement invariance, we conducted pairwise CFAs for the ZTPI-17, MAAS and SWLS. Regression analyses showed that PN predicted decreased LS in Poland and Japan. PP predicted increased LS in Spain. F predicted increased LS in Poland. DNTP predicted decreased LS in Poland. Mindfulness predicted decreased LS in Japan and increased LS in USA, Spain and Poland. Moreover, mediation analyses revealed that the DBTP partially mediated the relationship between mindfulness and LS in Spain and USA. The DNTP partially mediated the relationship between mindfulness and LS in Spain, Poland and Japan (opposite direction). The findings suggest that the association of TP, mindfulness and LS differs across the investigated countries as a function of culture.

History of Mild Traumatic Brain Injury Affects Static Balance under Complex Multisensory Manipulations.

A recent study in active-duty military in the Coast Guard suggested that lifetime experience with mild traumatic brain injury (mTBI) was associated with subtle deficits in postural control when exposed to multi-sensory discordance (i.e., rotating visual stimulation). The present study extended postural assessments to veterans recruited from the community. Service veterans completed the Defense Veteran Brain Injury Center TBI Screening Tool, Post-Traumatic Stress Disorder (PTSD) Checklist (PCL-5), and Neurobehavioral Symptom Inventory (NSI). Postural control was assessed using a custom-designed, virtual-reality-based device, which assessed center of pressure sway in response to six conditions designed to test sensory integration by systematically combining three visual conditions (eyes open, eyes closed, and rotating scene) with two somatosensory conditions (firm or foam surface). Veterans screening positive for lifetime experience of mTBI (mTBI+) displayed similar postural sway to veterans without a lifetime experience of mTBI (mTBI-) on basic assessment of eyes open or closed on a firm and foam surface. mTBI+ veterans displayed greater sway than mTBI- veterans in response to rotating visual stimuli while on a foam surface. Similar to previous research, degree of sway was affected by the number of lifetime experiences of mTBI. Increased postural sway was not related to PTSD, NSI, or balance-specific symptom expression. In summary, veterans who experienced mTBI over their lifetime exhibited dysfunction in balance control as revealed by challenging conditions with multi-sensory discordance. These balance-related signs were independent of self-reported balance-related symptoms or other symptom domains measured by the NSI, which can provide a method for exposing otherwise covert dysfunction long after the experience of mTBI.

Acute neurocognitive deficits in active duty service members following subconcussive blast exposure.

Military service members are frequently subjected to subconcussive blast events during training and deployment. Emerging evidence suggests blast exposures of these magnitudes may have long-term consequences for dimensions of cognitive function. Less is known about cognitive sequelae acutely following deployment-related subconcussive blast events. The current study addressed this knowledge gap by assessing the extent to which subconcussive blast exposure affected performance on the Automated Neuropsychological Assessment Metrics 4 TBI-MIL (ANAM). Baseline-referenced and normative comparisons of archival ANAM data were analyzed for a cohort of personnel who were exposed to blast (blast group; n = 27) and personnel who were not exposed to blast (no-blast group; n = 36) that were otherwise asymptomatic for a concussion. The blast group exhibited statistically significant lower scores compared to the no-blast group (between-subjects), baseline assessments (within-subjects), and an age-matched normative population. Normative comparisons revealed that the scores for the reaction time subtests (i.e., procedural and both simple reaction time tasks) were outside the range of normal functioning (1 SD) and reliable change indices revealed clinically meaningful change only for simple reaction time. The results highlight covert effects of subconcussive blast exposure that may warrant further monitoring in the immediate aftermath of a blast event.

Cardiorespiratory Response to Moderate Hypercapnia in Female College Students Expressing Behaviorally Inhibited Temperament.

Behaviorally inhibited (BI) temperament is marked by heightened behavioral sensitivity to environmental threats. The degree to which threat sensitivity is reflected in cardiorespiratory responses has been relatively unexplored. Female college students were exposed to modest hypercapnia (7.0% CO2) or ambient air (AA) while engaging in a computerized task with cued reinforcement features. All physiological variables except for blood pressure were processed in 4 min epochs corresponding to pre-exposure, exposure, and post-exposure. Primary respiratory measures were respiratory frequency (fb), tidal volume (VT), and minute ventilation (VE). Electrocardiograms (ECGs) were processed using ARTiiFACT software with resultant heart rate variability (HRV) measures in the frequency domain and time domain. Consistent with the literature, modest hypercapnia increased VT, Fb, and VE. No differences in respiratory parameters were detected between BI and non-behaviorally inhibited individuals (NI). For HRV in the time domain, RMSSD and NN50 values increased during CO2 inhalation which then returned to pre-exposure levels after CO2 cessation. Hypercapnia increased high frequency (HF) power which then recovered. BI exhibited reduced low frequency (LF) power during the pre-exposure period. For NI, LF power reduced over the subsequent phases ameliorating differences between BI and NI. Hypercapnia improved the task performance of BI. This is the largest study of female reactivity to hypercapnia and associated HRV to date. In general, hypercapnia increased time domain HRV and HF power, suggesting a strong vagal influence. Those expressing BI exhibited similar respiratory and HRV reactivity to NI despite inherently reduced LF power. Although 7% CO2 represents a mild challenge to the respiratory and cardiovascular systems, it is nonetheless sufficient to explore inherent difference in stress reactivity in those vulnerable to develop anxiety disorders.

Enhanced Acquisition and Retention of Conditioned Eyeblink Responses in Veterans Expressing PTSD Symptoms: Modulation by Lifetime History of Mild Traumatic Brain Injury.

Enhanced acquisition of eyeblink conditioning is observed in active duty military and veterans expressing PTSD symptoms (PTSD+) and those expressing temperamental vulnerabilities to develop PTSD after traumatic experiences, such as behaviorally inhibited temperament. There is a growing literature showing persistent cerebellar abnormalities in those experiencing mild traumatic brain injury (mTBI+) as well as linkages between mTBI and PTSD. With the dependency of eyeblink conditioning on cerebellar processes, the impact of mTBI on eyeblink conditioning in veterans expressing PTSD is unknown. The present study assessed eyeblink conditioning in veterans during two sessions separated by 1 week. With a focus on the accelerated learning of veterans expressing PTSD, training utilized a protocol which degrades learning through interspersing conditioned stimulus (CS) exposures amongst delay-type trials of CS and unconditional stimulus (US) co-terminating trials. Faster acquisition of the eyeblink conditioned responses (CR) was observed in PTSD during Week 1. The Week 2 assessment revealed an interaction of mTBI and PTSD, such that asymptotic performance of PTSD+ was greater than PTSD- among mTBI- veterans, whereas these groups did not differ in mTBI+ veterans. To further examine the relationship between enhanced sensitivity to acquire eyeblink conditioning and PTSD, cluster analysis was performed based on performance across training sessions. Those with enhanced sensitivity to acquire eyeblink conditioned responses expressed more PTSD symptoms, which were specific to Cluster C symptoms of avoidance, in addition to greater behavioral inhibition. These results support the continued investigation of the conditioned eyeblink response as a behavioral indicator of stress-related psychopathology.

Partial Predictability in Avoidance Acquisition and Expression of Wistar-Kyoto and Sprague-Dawley Rats: Implications for Anxiety Vulnerability in Uncertain Situations.

Individual differences or vulnerabilities must exist which bias some individuals toward psychopathology while others remain resilient in the face of trauma. Recent work has studied the effects of uncertainty on individuals expressing behavioral inhibition (BI). The current study extended this work with uncertainty to Wistar Kyoto (WKY) rats which are a behaviorally inhibited inbred strain that models learning vulnerabilities for anxiety disorders and posttraumatic stress disorder (PTSD). WKY rats exhibit superior avoidance performance in a signaled bar press avoidance task in which a tone conditioned stimulus (CS) signals a foot shock unconditional stimulus (US) when compared with non-inhibited Sprague-Dawley (SD) rats. In addition, WKY rats express enhanced eyeblink conditioning. Recent work with behaviorally inhibited humans has indicated that this enhanced eyeblink conditioning is more evident in conditions that insert CS- or US-alone trials into CS-US paired training, resulting in uncertain and suboptimal learning conditions. The current study examined the effects of partial predictability training, in which the CS signaled the US only one-half of the time, on the acquisition and expression of avoidance. Standard training with a fixed 60-s CS which predicted shock on 100% of trials was compared with training in which the CS predicted shock on 50% of trials (partial predictability) using a pseudorandom schedule. As expected, WKY rats acquired avoidance responses faster and to a greater degree than SD rats. Partial predictability of the US essentially reduced SD rats to escape responding. Partial predictability also reduced avoidance in WKY rats; however, adjusting avoidance rates for the number of potential pairings of the CS and US early in training suggested a similar degree of avoidance expression late in the last session of training. Enhanced active avoidance expression, even in uncertain learning conditions, can be interpreted as behaviorally inhibited WKY rats responding to the expectancy of the shock by avoiding, whereas non-inhibited SD rats were responding to the presence of the shock by escaping. Future work should explore how WKY and SD rats as well as behaviorally inhibited humans acquire and extinguish avoidance responses in uncertain learning situations.

Toward an assessment of escape/avoidance coping in depression.

Models of animal behavior suggest that anxiety and major depressive disorder (MDD) may be characterized by different profiles of escape and avoidance behavior. However, the literature on coping strategies fails to distinguish between avoidance and escape coping patterns, instead grouping escape behaviors into the larger category of avoidant coping. We argue that investigating both escape and avoidance coping behavior in those with anxiety and depression may reveal distinct behavioral profiles, whereas the current conceptual framework has failed to find significant differences coping style.

Reduced avoidance coping in male, but not in female rats, after mild traumatic brain injury: Implications for depression.

Although there is evidence that traumatic brain injury (mTBI) induces emotional sequelae in rats, it is unclear whether the phenotype is reminiscent of major depressive disorder (MDD) or posttraumatic stress disorder (PTSD). Three behavioral protocols with oppositional indicators for MDD or PTSD were assessed: acoustic startle responses (ASRs), eyeblink conditioning, and instrumental escape/avoidance (E/A) learning. Female and male rats were exposed to lateral fluid percussion injury (LFPi) consistent with mild TBI (mTBI) or sham (SHAM) surgery. Experiment 1 suggested that the acquisition of the classically conditioned eyeblink responses was unaffected by mTBI infemale and male rats. In Experiment 2, male and female mTBI rats acquired instrumental escape responses similar to their SHAM counterparts. Avoidance expression of female mTBI rats did not differ appreciably from female SHAM rats. However, male mTBI rats expressed avoidance at a lower rate than male SHAM rats over training. Poor coping in male rats emerged with repeated exposure to stress, suggesting that depressive behaviors in mTBI develop over time and with continued demand from stress. Severely attenuated ASRs were evident in female and male mTBI rats compared to respective SHAM rats throughout testing across the two experiments. Overall, signs among the three bidirectional assessments during the subacute period after mTBI were more indicative of MDD-like, than PTSD-like sequelae.

Inhibited Personality Temperaments Translated Through Enhanced Avoidance and Associative Learning Increase Vulnerability for PTSD.

Although many individuals who experience a trauma go on to develop post-traumatic stress disorder (PTSD), the rate of PTSD following trauma is only about 15-24%. There must be some pre-existing conditions that impart increased vulnerability to some individuals and not others. Diathesis models of PTSD theorize that pre-existing vulnerabilities interact with traumatic experiences to produce psychopathology. Recent work has indicated that personality factors such as behavioral inhibition (BI), harm avoidance (HA), and distressed (Type D) personality are vulnerability factors for the development of PTSD and anxiety disorders. These personality temperaments produce enhanced acquisition or maintenance of associations, especially avoidance, which is a criterion symptom of PTSD. In this review, we highlight the evidence for a relationship between these personality types and enhanced avoidance and associative learning, which may increase risk for the development of PTSD. First, we provide the evidence confirming a relationship among BI, HA, distressed (Type D) personality, and PTSD. Second, we present recent findings that BI is associated with enhanced avoidance learning in both humans and animal models. Third, we will review evidence that BI is also associated with enhanced eyeblink conditioning in both humans and animal models. Overall, data from both humans and animals suggest that these personality traits promote enhanced avoidance and associative learning, as well as slowing of extinction in some training protocols, which all support the learning diathesis model. These findings of enhanced learning in vulnerable individuals can be used to develop objective behavioral measures to pre-identify individuals who are more at risk for development of PTSD following traumatic events, allowing for early (possibly preventative) intervention, as well as suggesting possible therapies for PTSD targeted on remediating avoidance or associative learning. Future work should explore the neural substrates of enhanced avoidance and associative learning for behaviorally inhibited individuals in both the animal model and human participants.

Healthy Active Duty Military with Lifetime Experience of Mild Traumatic Brain Injury Exhibits Subtle Deficits in Sensory Reactivity and Sensory Integration During Static Balance.

Postural control and stress reactivity were investigated in active duty coast guard personnel to determine whether they are sensitive to lifetime effects of mild traumatic brain injury (mTBI). A custom-designed and validated virtual reality-based computerized posturography device was used to assess postural stability, whereas emotional reactivity was assessed using the acoustic startle response (ASR), and neurocognitive performance was assessed using the defense-automated neurobehavioral assessment (DANA). It was hypothesized that residual and subtle postural control imbalance and deficits in cognitive and sensory reactivity would be evident in those reporting multiple lifetime mTBI. Active duty military personnel (N = 36; 7 females and 29 males) with no Deployment Limiting Medical Condition were recruited and tested on all assessments. Medical history information provided a history of head injury. Thirty-nine percent of participants reported having a previous mTBI (nine reporting one and five reporting more than one incident). No participant had experienced a head injury within the past year and all were symptom free. A significant effect of number of mTBI was found in the postural assessment (p = 0.002). Lifetime mTBI was associated with suppressed ASR magnitude (p = 0.03) but did not affect neurocognitive performance. The current findings provide new insight into ongoing controversies concerning sensitivity to functional deficits following mTBI and when the window for treatment or restoration ends.

Facilitated acquisition of the classically conditioned eyeblink response in active duty military expressing posttraumatic stress disorder symptoms.

OBJECTIVE: Learning diathesis models underscore the role of hyper-conditioning in the development of PTSD following trauma exposure. Eyeblink classical conditioning is one method of examining associative learning biases independent of fear and threat produced by trauma. Facilitated learning is apparent in individuals self-expressing PTSD symptoms, as well as behaviorally inhibited (BI) temperament, a vulnerability factor for PTSD. Here, we examine eyeblink conditioning in active duty military personnel and relate learning with PTSD symptomology. METHOD: Volunteers were 83 active duty United States Coast Guard personnel (18 females) recruited from small boat stations. Personnel were administered the PTSD Checklist (PCL) to assess current PTSD symptoms using DSM-IV criteria. BI temperament was assessed with the Adult Measure of Behavioural Inhibition (AMBI). Eyeblink conditioning was conducted using a partial reinforcement schedule, whereby paired trials (500-ms pure tone conditioned stimulus co-terminating with a 50-ms air-puff unconditional stimulus) were interpolated with 50% CS-alone trials. RESULTS: Consistent with previous work, there was a high degree of concordance between BI and incidence of PTSD. Further, PTSD was associated with faster learning during the acquisition period, with conditioned responding sustained through the extinction period. CONCLUSIONS: These results reinforce the relationship between BI and PTSD in an active duty military sample, supporting previous observations in veteran and civilian samples. The conditioning data are consistent with predictions derived from a learning diathesis model of stress and anxiety, suggesting facilitated associative learning may represent an additional vulnerability for the development and maintenance of stress-related pathology.

Neurocognitive and Fine Motor Deficits in Asymptomatic Adolescents during the Subacute Period after Concussion.

Adolescents are at high risk for sustaining concussions. There is considerable controversy regarding the sensitivity of neurocognitive tests to detect and track dysfunction in the aftermath of concussion. Two neurocognitive test batteries were compared during the subacute phase of recovery from concussion to determine sensitivity to concussion. Adolescents (ages 11-17 years) with a concussion diagnosis (eight males, seven females, 9-69 days after injury) were recruited through a concussion clinic and compared with community nonconcussed volunteers (11 males, three females). Adolescents completed the online version of the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) on a desktop computer and the Defense Automated Neurobehavioral Assessment (DANA) on a handheld device, as well as the Grooved Pegboard Test, which assessed manual dexterity and motor speed. There were no differences in self-reported symptoms on the Post-Concussion Symptom Scale comparing concussed and nonconcussed adolescents. No significant between-groups differences were observed in ImPACT performance. Performance deficits were apparent for the DANA assessment, reflecting lower throughput scores for simple reaction time and response inhibition parameters in those with concussion. Concussed adolescents also had slower Grooved Pegboard Test performance when using the nondominant hand. Both the DANA test battery and the Grooved Pegboard Test appear to have promise as tools to detect persistent cognitive and motor dysfunction in the subacute period after concussion.

Stress-Related Mental Health Symptoms in Coast Guard: Incidence, Vulnerability, and Neurocognitive Performance.

U.S. Coast Guard (CG) personnel face occupational stressors (e.g., search and rescue) which compound daily life stressors encountered by civilians. However, the degree CG personnel express stress-related mental health symptoms of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) is understudied as a military branch, and little is known concerning the interplay of vulnerabilities and neurocognitive outcomes in CG personnel. The current study addressed this knowledge gap, recruiting 241 active duty CG personnel (22% female) to assess mental health, personality, and neurocognitive function. Participants completed a battery of scales: PTSD Checklist with military and non-military prompts to screen for PTSD, Psychological Health Questionnaire 8 for MDD, and scales for behaviorally inhibited (BI) temperament, and distressed (Type D) personality. Neurocognitive performance was assessed with the Defense Automated Neurobehavioral Assessment (DANA) battery. Cluster scoring yielded an overall rate of PTSD of 15% (95% CI: 11-20%) and 8% (95% CI: 3-9%) for MDD. Non-military trauma was endorsed twice that of military trauma in those meeting criteria for PTSD. Individual vulnerabilities were predictive of stress-related mental health symptoms in active duty military personnel; specifically, BI temperament predicted PTSD whereas gender and Type D personality predicted MDD. Stress-related mental health symptoms were also associated with poorer reaction time and response inhibition. These results suggest rates of PTSD and MDD are comparable among CG personnel serving Boat Stations to those of larger military services after combat deployment. Further, vulnerabilities distinguished between PTSD and MDD, which have a high degree of co-occurrence in military samples. To what degree stress-related mental healthy symptoms and attendant neurocognitive deficits affect operational effectiveness remains unknown and warrant future study.

Startle suppression after mild traumatic brain injury is associated with an increase in pro-inflammatory cytokines, reactive gliosis and neuronal loss in the caudal pontine reticular nucleus.

Mild traumatic brain injury (mTBI) can produce somatic symptoms such as headache, dizziness, fatigue, sleep disturbances and sensorimotor dysfunction. Sensorimotor function can be measured by tests such as the acoustic startle reflex (ASR), an evolutionarily conserved defensive response to a brief yet sharp acoustic stimulus. mTBI produces a long-lasting suppression of ASR in rodents and humans; however, the mechanism of this suppression is unknown. The present study examined whether inflammatory processes in the brainstem (particularly the caudal pontine reticular nucleus, PnC) could account for the suppression of ASR after mTBI, because the PnC is an essential nucleus of the ASR circuit. Furthermore, while inflammation after mTBI is commonly observed in brain regions proximal to the site of impact (cortex and hippocampus), the effects of mTBI in brainstem structures remains largely understudied. The present study demonstrated a suppression of ASR one day after injury and lasting at least three weeks after an mTBI, replicating previous findings. Within the PnC, transient elevations of IL-1ß and TNF-α mRNA were observed at one day after injury, while IL-1α mRNA exhibited a delayed increase at three weeks after injury. Reactive gliosis (via IBA-1-ir for microglia and GFAP-ir for astrocytes) were also observed in the PnC, at one day and seven days after injury, respectively. Finally, the number of giant neurons (the major functional cell population in the PnC) was decreased three weeks after injury. The results indicate that glial activation precedes neuronal loss in the PnC, and correlates with the behavioral suppression of the ASR. The results also raise implications for brainstem involvement in the development of post-traumatic symptoms.

Cerebellar response to familiar and novel stimuli: An fMRI study.

Historically known for its key contribution to motor behavior, the cerebellum continues to break boundaries. Researchers have demonstrated the cerebellum also plays a role in learning, memory, and more recent evidence for contributions in language, attention, working memory, emotions, and social processes. Here, we present a study that adds to the list of nonmotor processes of the cerebellum. We used images of faces and outdoor scenes to examine the cerebellar response to familiar and novel stimuli. Participants were familiarized with a subset of stimuli, and then underwent functional MRI (fMRI) where they were presented with the previously stimuli and new stimuli while making "old" and "new" judgment. In a familiar versus novel contrast, familiar stimuli (faces and scenes combined) activated bilateral regions of the cerebellum including I-IV, V, VI, Crus I, and Crus II. When separated by type, familiar faces had greater activation of bilateral I-IV than novel faces. These results demonstrate the cerebellar role in determining familiarity and contribute to continuing research supporting cerebellar contributions to nonmotor processes. (PsycINFO Database Record

Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury.

Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

Exposure to morphine-associated cues increases mu opioid receptor mRNA expression in the nucleus accumbens of Wistar Kyoto rats.

The Wistar-Kyoto (WKY) rat has been proposed as a model of anxiety vulnerability as it exhibits pronounced behavioral inhibition, passive avoidance, exaggerated startle response, enhanced HPA-axis activation, and active avoidance that is resistant to extinction. Accumulating evidence suggests that WKY rats respond differently to rewarding stimuli when compared to outbred strains of rat. Conditioned responding to drug-associated cues is linked with alterations in the activation of mu opioid receptors (MOR) and kappa opioid receptors (KOR) in the nucleus accumbens (NAc). Furthermore, alterations in KOR expression/activation in the NAc of WKY rats are implicated in the regulation of some of the components that make up the unique behavioral phenotype of this strain. The purpose of this study was to extend upon previous work from our laboratory by investigating conditioned morphine reward in adult male WKY and SD rats, and to examine levels of KOR mRNA and MOR mRNA in the NAc at baseline and after acquisition of morphine CPP. Our results demonstrate that SD rats displayed morphine-induced CPP to each of the six doses of morphine tested (0.5, 1.25, 2.5, 5, 7.5, or 10mg/kg). Interestingly, WKY rats demonstrated CPP for only the 1.25, 2.5, and 5mg/kg doses, yet no preference at the lowest (0.5mg/kg) or highest (7.5 and 10mg/kg) doses. qPCR analysis of MOR and KOR in the NAc revealed no strain differences in basal levels of MOR, but higher levels of KOR in WKY rats compared to those of SD rats. Interestingly, after completion of the CPP task, WKY rats had overall higher levels of NAc MOR mRNA compared to SD rats; the initial basal differences in NAc KOR levels persisted without change due to CPP in either strain. These results demonstrate that the WKY rat exhibits a unique pattern of behavioral responding to morphine and implicates differences in NAc KOR signaling as a potential source of aversion to higher doses of morphine. Additionally, the CPP-induced upregulation of NAc MOR mRNA in WKY rats warrants further investigation in terms of its potential role as a factor constituting a unique vulnerability to subsequent drug exposure.

Paired-housing selectively facilitates within-session extinction of avoidance behavior, and increases c-Fos expression in the medial prefrontal cortex, in anxiety vulnerable Wistar-Kyoto rats.

OBJECTIVE: The perseveration of avoidance behavior, even in the absence of once threatening stimuli, is a key feature of anxiety and related psychiatric conditions. This phenomenon can be observed in the Wistar-Kyoto (WKY) rat which, in comparison to outbred controls, demonstrates impaired extinction of avoidance behavior. Also characteristic of the WKY rat is abnormalities of the neurocircuitry and neuroplasticity of the medial prefrontal cortex (mPFC). One means of reducing physiological responses to anxiety, and conditioned fear, in social species is the presence of a conspecific animal. The current study investigates whether or not pair-housed WKY rats would show facilitated extinction of avoidance in comparison to individual-housed WKY rats, and whether or not pair-housing influences mPFC activation during lever-press avoidance. METHODS: Male WKY rats were assigned to individual-housed and pair-housed conditions. Rats were trained in lever-press avoidance. Each session of lever-press avoidance consisted of 20 trials, where pressing a lever in response to a warning tone prevented foot-shocks. Rats received 12 acquisition sessions over 4weeks; followed by 6 extinction sessions over 2weeks, where foot-shocks ceased to be delivered. Brains were harvested 90min after trials 1 and 10 of extinction sessions 1 and 6, and mPFC sections underwent c-Fos staining as a measure of activation. RESULTS: Pair-housed rats showed facilitated lever-press avoidance extinction rates, but the main cause for this overall difference was a selective facilitation of within-session extinction. Similar to individual-housed rats, pair-housed rats continued to avoid during trial 1 of extinction even when the avoidance responding had been significantly reduced by the end of the previous session. Pair-housed rats sacrificed on trial 1 showed greater c-Fos expression in the anterior cingulate cortex and prelimbic cortex subregions of the mPFC compared individual-housed rats sacrificed on trial 1. CONCLUSION: This data shows pair-housing to facilitate the extinction of avoidance, and to influence activity of the mPFC, in WKY rats. Despite this environmental manipulation, the pair-housed WKY rats continued to show avoidance responding on trial 1 of extinction sessions. This demonstrates that within-session extinction can be dissociated from between-session extinction-resistance in WKY rats. Furthermore, it suggests the individual-housing of WKY rats selectively slows within-session extinction, possibly by reducing neuronal activity of the mPFC during the testing situation.

Exaggerated acquisition and resistance to extinction of avoidance behavior in treated heroin-dependent men.

OBJECTIVE: Addiction is often conceptualized as a behavioral strategy for avoiding negative experiences. In rodents, opioid intake has been associated with abnormal acquisition and extinction of avoidance behavior. Here, we tested the hypothesis that these findings would generalize to human opioid-dependent subjects. METHOD: Adults meeting DSM-IV criteria for heroin dependence and treated with opioid medication (n = 27) and healthy controls (n = 26) were recruited between March 2013 and October 2013 and given a computer-based task to assess avoidance behavior. For this task, subjects controlled a spaceship and could either gain points by shooting an enemy spaceship or hide in safe areas to avoid on-screen aversive events. Hiding duration during different periods of the task was used to measure avoidance behavior. RESULTS: While groups did not differ on escape responding (hiding) during the aversive event, heroin-dependent men (but not women) made more avoidance responses during a warning signal that predicted the aversive event (analysis of variance, sex × group interaction, P = .007). Heroin-dependent men were also slower to extinguish the avoidance response when the aversive event no longer followed the warning signal (P = .011). This behavioral pattern resulted in reduced opportunity to obtain reward without reducing risk of punishment. Results suggest that, in male patients, differences in avoidance behavior cannot be easily explained by impaired task performance or by exaggerated motor activity. CONCLUSIONS: This study provides evidence for abnormal acquisition and extinction of avoidance behavior in opioid-dependent patients. Interestingly, data suggest that abnormal avoidance is demonstrated only by male patients. Findings shed light on cognitive and behavioral manifestations of opioid addiction and may facilitate development of therapeutic approaches to help affected individuals.