- Sigma-1 receptor antagonist, PD144418, selectively reduces female motivation for food during negative energy balance. [Journal Article]
- BBBehav Brain Res 2019 Jul 17; :112087
- Sigma-1 (σ1) receptors have been investigated for their involvement in learning, rewarding and motivational processes. PD144418, a σ1 receptor antagonist, has been found to produce a dose-dependent a…
Sigma-1 (σ1) receptors have been investigated for their involvement in learning, rewarding and motivational processes. PD144418, a σ1 receptor antagonist, has been found to produce a dose-dependent attenuation of locomotor activity induced by cocaine, and by itself, does not suppress basal locomotor activity in mice. Moreover, PD144418 decreases the motivational effort of a food-reinforced behavior in male rats, without altering appetite or food palatability. It remains unknown whether the PD144418 can alter the motivational effort of a food-reinforced behavior in response to altered energy homeostasis, as is the case under 24 -h food deprivation. Additionally, while the previous experiments indicate effects in male rats, there has been no research examining the effects of PD144418, or any other σ1 receptor antagonist, on motivational aspects of feeding in females. The present study examined the effects of PD144418 on motivational aspects of feeding in male and female rats using an operant task under sated or food deprived conditions. Results indicated that when animals are sated, at the highest dose (10 μmol/kg), under a progressive ratio (PR) reinforcement schedule, PD144418 significantly attenuated the breakpoint and the number of active lever responses for sucrose pellets in both males and females. When animals are in a state of energy deficit, as is the case following 24-hr food deprivation, PD144418 does not alter motivationally driven operant responding as measured by the breakpoint in either sex but does alter the number of earned reinforcers responses in females.
- Timberlake's Behavior Systems: A Paradigm Shift toward an Ecological Approach. [Review]
- BPBehav Processes 2019 Jul 16; :103892
- Timberlake's Behavior Systems model constitutes a discontinuity in theoretical and empirical consequences of traditional approaches to the experimental study of behavior, such as operant as well as c…
Timberlake's Behavior Systems model constitutes a discontinuity in theoretical and empirical consequences of traditional approaches to the experimental study of behavior, such as operant as well as classical conditioning. Here we consider the synergy of an animal-centered approach and acknowledge that niche-related behaviors as functional activities create synergy with Gibson's ecological approach, in at least three terms. These are: an ecological stance for learning and behavior, hierarchical organization of behavior systems, and affordances implied in the process of tuning experimental procedures. The ideas expressed herein favor a paradigm shift toward an ecological approach to behavioral science.
- Sham surgeries for central and peripheral neural injuries persistently enhance pain-avoidance behavior as revealed by an operant conflict test. [Journal Article]
- PAINPain 2019 Jun 05
- Studies using rodent models of neuropathic pain employ sham surgery control procedures that cause deep tissue damage. Sham surgeries would thus be expected to induce potentially long-lasting postsurg…
Studies using rodent models of neuropathic pain employ sham surgery control procedures that cause deep tissue damage. Sham surgeries would thus be expected to induce potentially long-lasting postsurgical pain, but little evidence for such pain has been reported. Operant tests of voluntary behavior can reveal negative motivational and cognitive aspects of pain that may provide sensitive tools for detecting pain-related alterations. In a previously described operant mechanical conflict (MC) test involving lengthy familiarization and training, rodents freely choose to either escape from a brightly lit chamber by crossing sharp probes or refuse to cross. Here, we describe a brief (2-day) MC protocol that exploits rats' innate exploratory response to a novel environment in order to detect persistently enhanced pain-avoidance behavior after sham surgeries for two neural injury models: thoracic spinal cord injury (SCI) and chronic constriction injury (CCI) of the sciatic nerve. Pitting the combined motivations to avoid the bright light and to explore the novel device against pain from crossing noxious probes disclosed a conflicting, hyperalgesia-related reluctance to repeatedly cross the probes after injury. Rats receiving standard sham surgeries demonstrated enhanced pain-like avoidance behavior compared to naive controls, and this behavior was similar to that of corresponding CCI or SCI rats weeks or months after injury. In the case of sham surgery for SCI, video analysis of voluntary exploratory behavior directed at the probes revealed enhanced forepaw withdrawal responses. These findings have important implications for preclinical investigations into behavioral alterations and physiological mechanisms associated with postsurgical and neuropathic pain.
- Sign-tracking behavior is difficult to extinguish and resistant to multiple cognitive enhancers. [Journal Article]
- NLNeurobiol Learn Mem 2019 Jul 15; :107045
- The attribution of incentive-motivational value to drug-related cues underlies relapse and craving in drug addiction. One method of addiction treatment, cue-exposure therapy, utilizes repeated presen…
The attribution of incentive-motivational value to drug-related cues underlies relapse and craving in drug addiction. One method of addiction treatment, cue-exposure therapy, utilizes repeated presentations of drug-related cues in the absence of drug (i.e., extinction learning); however, its efficacy has been limited due to an incomplete understanding of extinction and relapse processes after cues have been imbued with incentive-motivational value. To investigate this, we used a Pavlovian conditioned approach procedure to screen for rats that attribute incentive-motivational value to reward-related cues (sign-trackers; STs) or those that do not (goal-trackers; GTs). In Experiment 1, rats underwent Pavlovian extinction followed by reinstatement and spontaneous recovery tests. For comparison, a separate group of rats underwent PCA training followed by operant conditioning, extinction, and tests of reinstatement and spontaneous recovery. In Experiment 2, three cognitive enhancers (sodium butyrate, D-cycloserine, and fibroblast growth factor 2) were administered following extinction training to facilitate extinction learning. STs but not GTs displayed enduring resistance to Pavlovian, but not operant, extinction and were more susceptible to spontaneous recovery. In addition, none of the cognitive enhancers tested affected extinction learning. These results expand our understanding of extinction learning by demonstrating that there is individual variation in extinction and relapse processes and highlight potential difficulties in applying extinction-based therapies to drug addiction treatment in the clinic.
- Effort Displayed During Appetitive Phase of Feeding Behavior Requires Infralimbic Cortex Activity and Histamine H1 Receptor Signaling. [Journal Article]
- FNFront Neurosci 2019; 13:577
- The chances to succeed in goal-directed behaviors, such as food or water-seeking, improve when the subject is in an increased arousal state. The appetitive phase of these motivated behaviors is chara…
The chances to succeed in goal-directed behaviors, such as food or water-seeking, improve when the subject is in an increased arousal state. The appetitive phase of these motivated behaviors is characterized by high levels of behavioral and vegetative excitation. The key decision of engaging in those particular behaviors depends primarily on prefrontal cortical areas, such as the ventromedial prefrontal cortex. We propose that the infralimbic cortex (ILC) located in the medial prefrontal cortex induces an increase in arousal during the appetitive phase of motivated behavior, and that this increase in arousal is, in turn, mediated by the activation of the brain histaminergic system, resulting in higher motivation for getting food rewards. To test this hypothesis, we conduct a progressive ratio operant conditioning to test the degree of motivation for food, while simultaneously manipulating the histaminergic system through pharmacologic interventions. We found that the behavioral responses to obtain food in hungry rats were disrupted when the ILC was inhibited through muscimol infusion, blocking brain H1 histamine receptors by intracerebroventricular infusion of pyrilamine or by satiety. In contrast, the consummatory behavior was not affected by ILC inhibition. The extracellular histamine levels in the ILC were increased in direct correlation with the degree of motivation measured in the progressive ratio test. ILC inhibition also prevented this increase in histamine levels. The rise in extracellular histamine levels during the progressive ratio test was similar (ca. 200%) during the active or the resting period of the day. However, different basal levels are observed for these two periods. Our findings suggest that increased histamine levels during this behavior are not simply explained by the awaked state, but instead, there is a motivation-related release of histamine, suggestive of a specific form of brain activation. Serotonin (another critical component of the ascending arousal system) was also tested. Interestingly, changes in levels of this neuromodulator were not detected during the progressive ratio test. In conclusion, our results suggest that ILC activation and subsequent increase in brain histamine release are both necessary for the normal performance of a motivated behavior such as feeding.
- Indirect medium spiny neurons in the dorsomedial striatum regulate ethanol-containing conditioned reward seeking. [Journal Article]
- JNJ Neurosci 2019 Jul 17
- Adenosine 2A receptor (A2AR)-containing indirect medium spiny neurons (iMSNs) in the dorsomedial striatum (DMS) contribute to reward-seeking behaviors. However, those roles for ethanol-seeking behavi…
Adenosine 2A receptor (A2AR)-containing indirect medium spiny neurons (iMSNs) in the dorsomedial striatum (DMS) contribute to reward-seeking behaviors. However, those roles for ethanol-seeking behaviors remain unknown. To investigate ethanol-seeking behaviors, we used an ethanol-containing reward (10% ethanol and 10% sucrose solution, 10E10S). Upon conditioning with 10E10S, mice that initially only preferred 10% sucrose (10S), not 10E10S, showed a stronger preference for 10E10S. Then, we investigated whether the manipulation of the DMS-GPe iMSNs circuit alters the ethanol-containing reward (10E10S) seeking behaviors using the combination of pharmacologic and optogenetic approaches. DMS A2AR activation dampened operant conditioning-induced ethanol-containing reward, whereas A2AR antagonist abolished the effects of the A2AR agonist and restored ethanol-containing reward-seeking. Moreover, pre-ethanol exposure potentiated the A2AR-dependent reward-seeking. Interestingly, mice exhibiting ethanol-containing reward-seeking showed the reduction of the DMS iMSNs activity, suggesting that disinhibiting iMSNs decreases reward-seeking behaviors. In addition, we found that A2AR activation reversed iMSNs neural activity in the DMS. Similarly, optogenetic stimulation of the DMS-GPe iMSNs reduced ethanol-containing reward-seeking, whereas optogenetic inhibition of the DMS-GPe iMSNs reversed this change. Taken together, our study demonstrates that DMS A2AR and iMSNs regulate ethanol-containing reward-seeking behaviors.Significant StatementOur findings highlight the mechanisms of how operant conditioning develops the preference of ethanol-containing conditioned reward. Mice exhibiting ethanol-containing reward-seeking showed a reduction of the indirect medium spiny neuronal activity in the dorsomedial striatum. Pharmacological activation of adenosine A2A receptor (A2AR) or optogenetic activation of indirect medium spiny neurons dampened operant conditioned ethanol-containing reward-seeking, whereas inhibiting this neuronal activity restored ethanol-containing reward-seeking. Furthermore, repeated intermittent ethanol exposure potentiated A2AR-dependent reward-seeking. Therefore, our finding suggests that A2AR-containing indirect medium spiny neuronal activation reduces ethanol-containing reward-seeking, which may provide a potential therapeutic target for alcohol use disorder (AUD).
- Sex Differences in the Effect of Alcohol Drinking on Myelinated Axons in the Anterior Cingulate Cortex of Adolescent Rats. [Journal Article]
- BSBrain Sci 2019 Jul 16; 9(7)
- Cognitive deficits associated with teenage drinking may be due to disrupted myelination of prefrontal circuits. To better understand how alcohol affects myelination, male and female Wistar rats (n = …
Cognitive deficits associated with teenage drinking may be due to disrupted myelination of prefrontal circuits. To better understand how alcohol affects myelination, male and female Wistar rats (n = 7-9/sex/treatment) underwent two weeks of intermittent operant self-administration of sweetened alcohol or sweetened water early in adolescence (postnatal days 28-42) and we tested for macro- and microstructural changes to myelin. We previously reported data from the males of this study showing that alcohol drinking reduced myelinated fiber density in layers II-V of the anterior cingulate division of the medial prefrontal cortex (Cg1); herein, we show that myelinated fiber density was not significantly altered by alcohol in females. Alcohol drinking patterns were similar in both sexes, but males were in a pre-pubertal state for a larger proportion of the alcohol exposure period, which may have contributed to the differential effects on myelinated fiber density. To gain more insight into how alcohol impacts myelinated axons, brain sections from a subset of these animals (n = 6/sex/treatment) were used for microstructural analyses of the nodes of Ranvier. Confocal analysis of nodal domains, flanked by immunofluorescent-labeled contactin-associated protein (Caspr) clusters, indicated that alcohol drinking reduced nodal length-to-width ratios in layers II/III of the Cg1 in both sexes. Despite sex differences in the underlying cause (larger diameter axons after alcohol in males vs. shorter nodal lengths after alcohol in females), reduced nodal ratios could have important implications for the speed and integrity of neural transmission along these axons in both males and females. Alcohol-induced changes to myelinated axonal populations in the Cg1 may contribute to long-lasting changes in prefrontal function associated with early onset drinking.
- Highly improved quasi-two-dimensional oxide transistors via non-centrosymmetric nitrogen dioxide treatment: towards extremely low-process temperature and operant self-aligned coplanar structure. [Journal Article]
- AAACS Appl Mater Interfaces 2019 Jul 15
- Rapid degradations are typically encountered in low-temperature processed oxide thin-film transistors (TFTs) with a high indium composition and quasi-two-dimensional (Q2D) thin channel, owing to the …
Rapid degradations are typically encountered in low-temperature processed oxide thin-film transistors (TFTs) with a high indium composition and quasi-two-dimensional (Q2D) thin channel, owing to the breaking of numerous surface bonds of the Q2D oxide and the ineffectiveness of oxidation treatment. Strategically, a novel approach is proposed for the effective use of non-centrosymmetric nitrous oxide (NO2) as a reactive oxidizer gas for realizing the highly robust and rapid field-effect mobility properties of low-temperature-processed Q2D a-IZO TFTs. From the surface chemical analysis, it is found that NO2 stably reconstructs surface chemical bonding with NO3- ions by capturing the charged electrons and oxygen, and the regions with and without NO2 treatment display extreme differences in their electrical conductivity. Thus, a new process design can be suggested for the fabrication of self-aligned co-planar Q2D transistors, with the aim of scaling down and replacing conventional hydrogen treatment or ultraviolet irradiation. This concept is tactically designed considering the problematic aging effect and impact of the NO2 treatment. The self-aligned co-planar top-gate Q2D a-IZO TFTs exhibit outstanding device performance with a field-effect mobility of 30.1 cm2 V-1s-1 and a relatively low positive bias stress shift of 1.3 V at an extremely low process temperature of 80 oC.
- The effects of age and sex on the detection of pure tones by adult CBA/CaJ mice (Mus musculus). [Journal Article]
- JNJ Neurosci Res 2019 Jul 15
- Age-related hearing loss (ARHL) is a neurodegenerative disorder characterized by a gradual decrease in hearing sensitivity. Previous electrophysiological and behavioral studies have demonstrated that…
Age-related hearing loss (ARHL) is a neurodegenerative disorder characterized by a gradual decrease in hearing sensitivity. Previous electrophysiological and behavioral studies have demonstrated that the CBA/CaJ mouse strain is an appropriate model for the late-onset hearing loss found in humans. However, few studies have characterized hearing in these mice behaviorally using longitudinal methodologies. The goal of this research was to utilize a longitudinal design and operant conditioning procedures with positive reinforcement to construct audiograms and temporal integration functions in aging CBA/CaJ mice. In the first experiment, thresholds were collected for 8, 16, 24, 42, and 64 kHz pure tones in 30 male and 35 female CBA/CaJ mice. Similar to humans, mice had higher thresholds for high frequency tones than for low frequency pure tones across the lifespan. Female mice had better hearing acuity than males after 645 days of age. In the second experiment, temporal integration functions were constructed for 18 male and 18 female mice for 16 and 64 kHz tones varying in duration. Mice showed an increase in thresholds for tones shorter than 200 ms, reaching peak performance at shorter durations than other rodent species. Overall, CBA/CaJ mice experience ARHL for pure tones of different frequencies and durations, making them a good model for studies on hearing loss. These findings highlight the importance of using a wide range of stimuli and a longitudinal design when comparing presbycusis across different species.
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- The translational approach to apathy-like behavior in mice: from the practical point of view. [Review]
- PCPsychiatry Clin Neurosci 2019 Jul 14
- Apathy is a pervasive clinical phenomenon that deserves more attention at the translational and pre-clinical levels. To study apathy-like behavior in mice, we relied on an operational definition of a…
Apathy is a pervasive clinical phenomenon that deserves more attention at the translational and pre-clinical levels. To study apathy-like behavior in mice, we relied on an operational definition of apathy: the quantitative reduction of voluntary, goal-directed behaviors. We recently found that the chronic loss-of-function of a specific cell type (striatal dopamine receptor type 2-expressing medium spiny neurons, D2-MSNs) within a restricted region (the ventrolateral striatum, VLS) was sufficient to induce apathy-like behavior in a food-seeking operant task. We further demonstrated that VLS D2-MSNs are activated at the preparatory period and optogenetic inhibition of VLS D2-MSNs during that period resulted in transient decreases in instrumental motivation, strengthening the hypothesis that VLS D2-MSNs mediate apathy-like behavior in mice. Mice bearing VLS D2-MSN dysfunction can thus be regarded as an apathy model for future translational studies. This article is protected by copyright. All rights reserved.