Conditioned Emotional Response Research Articles

Functional lateralization in the medial prefrontal cortex control of contextual conditioned emotional responses in rats

A functional lateralization has been reported in control of emotional responses by the medial prefrontal cortex (mPFC). However, a hemisphere asymmetry in involvement of the mPFC in expression of fear conditioning responses has never been reported. Therefore, we investigated whether control by mPFC of freezing and cardiovascular responses during re-exposure to an aversively conditioned context is lateralized. For this, rats had guide cannulas directed to the mPFC implanted bilaterally or unilaterally in the right or left hemispheres. Vehicle or the non-selective synaptic inhibitor CoCl2 was microinjected into the mPFC 10 min before re-exposure to a chamber where the animals had previously received footshocks. A catheter was implanted into the femoral artery before the fear retrieval test for cardiovascular recordings. We observed that bilateral microinjection of CoCl2 into the mPFC reduced both the freezing behavior (enhancing locomotion and rearing) and arterial pressure and heart rate increases during re-exposure to the aversively conditioned context. Unilateral microinjection of CoCl2 into the right hemisphere of the mPFC also decreased the freezing behavior (enhancing locomotion and rearing), but without affecting the cardiovascular changes. Conversely, unilateral synaptic inhibition in the left mPFC did not affect either behavioral or cardiovascular responses during fear retrieval test. Taken together, these results suggest that the right hemisphere of the mPFC is necessary and sufficient for expression of freezing behavior to contextual fear conditioning. However, the control of cardiovascular responses and freezing behavior during fear retrieval test is somehow dissociated in the mPFC, being the former bilaterally processed.

Novel five-phase model for understanding the nature of misophonia, a conditioned aversive reflex disorder.

Background: Misophonia is a recently identified condition in which a person perceives a subtle stimulus (e.g., eating sounds, hair twirling) and has an intense, negative emotional response. Misophonia cannot be classified with established nosological systems. Methods: We present a novel five-phase model of misophonia from a cognitive-behavioral framework. This model identifies a learned reflex of the autonomic nervous system as the primary etiology and maintenance of misophonia. Phase one is anticipatory anxiety and avoidance. Phase two is a conditioned physical reflex (for example, the tensing of calf muscles) that develops through stimulus-response Pavlovian conditioning. Phase three includes intense negative emotional responses and accompanying physiological distress, thoughts, urges, and emotion-driven behavior. Phase four is the individual's coping responses to emotional distress, and phase five is the environmental response and resulting internal and external consequences of the coping behaviors. Each phase helps explain the maintenance of the response and the individual's impairment. Results: Anticipatory anxiety and avoidance of phase one contributes to an increased arousal and awareness of triggers, resulting in increased severity of the trigger experience. Both the Pavlovian-conditioned physical reflex of phase two and the emotion-driven behavior caused by the conditioned emotional response of phase three increase with in vivo exposure to triggers. Phase four includes internal and external coping behaviors to the intense emotions and distress, and phase five includes the consequences of those behaviors. Internal consequences include beliefs fiveand new emotions based on environmental responses to anger and panic. For example, the development of emotions such as shame and guilt, and beliefs regarding how 'intolerable' the trigger is. Conclusions: We assert misophonia is a multi-sensory condition and includes anticipatory anxiety, conditioned physical reflexes, intense emotional and physical distress, subsequent internal and external responses, and environmental consequences.

Novel five-phase model for understanding the nature of misophonia, a conditioned aversive reflex disorder

Background: Misophonia is a recently identified condition in which a person perceives a subtle stimulus (e.g., eating sounds, hair twirling) and has an intense, negative emotional response. Misophonia cannot be classified with established nosological systems. Methods: We present a novel five-phase model of misophonia from a cognitive-behavioral framework. This model identifies a learned reflex of the autonomic nervous system as the primary etiology and maintenance of misophonia. Phase one is anticipatory anxiety and avoidance. Phase two is a conditioned physical reflex (for example, the tensing of calf muscles) that develops through stimulus-response Pavlovian conditioning. Phase three includes intense negative emotional responses and accompanying physiological distress, thoughts, urges, and emotion-driven behavior. Phase four is the individual’s coping responses to emotional distress, and phase five is the environmental response and resulting internal and external consequences of the coping behaviors. Each phase helps explain the maintenance of the response and the individual’s impairment. Results: Anticipatory anxiety and avoidance of phase one contributes to an increased arousal and awareness of triggers, resulting in increased severity of the trigger experience. Both the Pavlovian-conditioned physical reflex of phase two and the emotion-driven behavior caused by the conditioned emotional response of phase three increase with in vivo exposure to triggers. Phase four includes internal and external coping behaviors to the intense emotions and distress, and phase 5 includes the consequences of those behaviors. Internal consequences include beliefs and new emotions based on environmental responses to anger and panic. For example, the development of emotions such as shame and guilt, and beliefs regarding how ‘intolerable’ the trigger is. Conclusions: We assert misophonia is a multi-sensory condition and includes anticipatory anxiety, conditioned physical reflexes, intense emotional and physical distress, subsequent internal and external responses, and environmental consequences.

Novel five-phase model for understanding the nature of misophonia, a conditioned aversive reflex disorder

Background: Misophonia is a recently identified condition in which a person perceives a subtle stimulus (e.g., eating sounds, hair twirling) and has an intense, negative emotional response. Misophonia cannot be classified with established nosological systems. Methods: We present a novel five-phase model of misophonia from a cognitive-behavioral framework. This model identifies a learned reflex of the autonomic nervous system as the primary etiology and maintenance of misophonia. Phase one is anticipatory anxiety and avoidance. Phase two is a conditioned physical reflex (for example, the tensing of calf muscles) that develops through stimulus-response Pavlovian conditioning. Phase three includes intense negative emotional responses and accompanying physiological distress, thoughts, urges, and emotion-driven behavior. Phase four is the individual’s coping responses to emotional distress, and phase five is the environmental response and resulting internal and external consequences of the coping behaviors. Each phase helps explain the maintenance of the response and the individual’s impairment. Results: Anticipatory anxiety and avoidance of phase one contributes to an increased arousal and awareness of triggers, resulting in increased severity of the trigger experience. Both the Pavlovian-conditioned physical reflex of phase two and the emotion-driven behavior caused by the conditioned emotional response of phase three increase with in vivo exposure to triggers. Phase four includes internal and external coping behaviors to the intense emotions and distress, and phase 5 includes the consequences of those behaviors. Internal consequences include beliefs and new emotions based on environmental responses to anger and panic. For example, the development of emotions such as shame and guilt, and beliefs regarding how ‘intolerable’ the trigger is. Conclusions: We assert misophonia is a multi-sensory condition and includes anticipatory anxiety, conditioned physical reflexes, intense emotional and physical distress, subsequent internal and external responses, and environmental consequences.

Competing contextual processes rely on the infralimbic and prelimbic medial prefrontal cortices in the rat.

Ambiguous relationships between events may be established using interference procedures such as latent inhibition, extinction or counterconditioning. Under these conditions, the retrieval of individual associations between a stimulus and outcome is affected by contextual cues. To examine the roles of the dorsal (prelimbic) and ventral (infralimbic) medial prefrontal cortex in the contextual modulation of such associations, we investigated the context specificity of latent inhibition. Male Lister hooded rats were pre-exposed to two separate stimuli, one in each of two distinct contexts. Both stimuli were then paired with the delivery of mild foot-shock in the same one of these contexts. Finally, the strength of the resultant conditioned emotional response (CER) to each stimulus was assessed in each context. For the sham-operated control rats, the CER was attenuated for each stimulus when it was tested in the context in which it had been pre-exposed. Rats who had received lesions to the infralimbic cortex showed this effect only in the conditioning context, whereas rats with lesions to the prelimbic cortex showed the effect only in the context in which conditioning had not taken place. These findings indicate that infralimbic and prelimbic cortices play distinct, and competing, roles in the contextual modulation of initial and later learning.

Conditioned Emotional Response

Conditioned Emotional Response

Impairing memory reconsolidation with propranolol in healthy and clinical samples: a meta-analysis.

BackgroundReconsolidation impairment using propranolol is a novel intervention for mental disorders with an emotional memory at their core. In this systematic review and meta-analysis, we examined the evidence for this intervention in healthy and clinical adult samples.MethodsWe searched 8 databases for randomized, double-blind studies that involved at least 1 propranolol group and 1 placebo group. We conducted a meta-analysis of 14 studies (n = 478) in healthy adults and 12 studies in clinical samples (n = 446).ResultsCompared to placebo, reconsolidation impairment under propranolol resulted in reduced recall of aversive material and cue-elicited conditioned emotional responses in healthy adults, as evidenced by an effect size (Hedges g) of −0.51 (p = 0.002, 2-tailed). Moreover, compared to placebo, reconsolidation impairment under propranolol alleviated psychiatric symptoms and reduced cue-elicited reactivity in clinical samples with posttraumatic stress disorder, addiction or phobia (g = −0.42, p = 0.010).LimitationsMethodological differences between studies posed an obstacle for identifying sources of heterogeneity.ConclusionReconsolidation impairment is a robust, well-replicated phenomenon in humans. Its clinical use is promising and deserves further controlled investigation.

Hippocampal Disinhibition Reduces Contextual and Elemental Fear Conditioning While Sparing the Acquisition of Latent Inhibition

Hippocampal neural disinhibition, i.e., reduced GABAergic inhibition, is a key feature of schizophrenia pathophysiology. The hippocampus is an important part of the neural circuitry that controls fear conditioning and can also modulate prefrontal and striatal mechanisms, including dopamine signaling, which play a role in salience modulation. Consequently, hippocampal neural disinhibition may contribute to impairments in fear conditioning and salience modulation reported in schizophrenia. Therefore, we examined the effect of ventral hippocampus (VH) disinhibition in male rats on fear conditioning and salience modulation, as reflected by latent inhibition (LI), in a conditioned emotional response (CER) procedure. A flashing light was used as the conditioned stimulus (CS), and conditioned suppression was used to index conditioned fear. In experiment 1, VH disinhibition via infusion of the GABA-A receptor antagonist picrotoxin before CS pre-exposure and conditioning markedly reduced fear conditioning to both the CS and context; LI was evident in saline-infused controls but could not be detected in picrotoxin-infused rats because of the low level of fear conditioning to the CS. In experiment 2, VH picrotoxin infusions only before CS pre-exposure did not affect the acquisition of fear conditioning or LI. Together, these findings indicate that VH neural disinhibition disrupts contextual and elemental fear conditioning, without affecting the acquisition of LI. The disruption of fear conditioning resembles aversive conditioning deficits reported in schizophrenia and may reflect a disruption of neural processing both within the hippocampus and in projection sites of the hippocampus.

Analysis of memory modulation by conditioned stimuli.

Conditioned stimuli (CS) have multiple psychological functions that can potentially contribute to their effect on memory formation. It is generally believed that CS-induced memory modulation is primarily due to conditioned emotional responses, however, well-learned CSs not only generate the appropriate behavioral and physiological reactions required to best respond to an upcoming unconditioned stimulus (US), but they also serve as signals that the US is about to occur. Therefore, it is possible that CSs can impact memory consolidation even when their ability to elicit conditioned emotional arousal is significantly reduced. To test this, male Sprague–Dawley rats trained on a signaled active avoidance task were divided into “Avoider” and “Non-Avoider” subgroups on the basis of percentage avoidance after 6 d of training. Subgroup differences in responding to the CS complex were maintained during a test carried out in the absence of the US. Moreover, the subgroups displayed significant differences in stress-induced analgesia (hot-plate test) immediately after this test, suggesting significant subgroup differences in conditioned emotionality. Importantly, using the spontaneous object recognition task, it was found that immediate post-sample exposure to the avoidance CS complex had a similar enhancing effect on object memory in the two subgroups. Therefore, to our knowledge, this is the first study to demonstrate that a significant conditioned emotional response is not necessary for the action of a predictive CS on modulation of memory consolidation.

Differential modulation of the contextual conditioned emotional response by CB1 and TRPV1 receptors in the ventromedial prefrontal cortex: Possible involvement of NMDA/nitric oxide-related mechanisms.

Blockade of cannabinoid CB1 or vanilloid TRPV1 receptors in the ventromedial prefrontal cortex of rats respectively increases or decreases the conditioned emotional response during re-exposure to a context previously paired with footshocks. Although these mechanisms are unknown, they may involve local modulation of glutamatergic and nitrergic signaling. We investigated whether these mechanisms are involved in the reported effects of CB1 and TRPV1 modulation in the ventromedial prefrontal cortex. Freezing behavior and autonomic parameters were recorded during the conditioned response expression. The CB1 receptors antagonist NIDA, or the TRPV1 agonist capsaicin (CPS) in the ventromedial prefrontal cortex increased the conditioned emotional response expression, and these effects were prevented by TRPV1 and CB1 antagonism, respectively. The increased conditioned emotional response evoked by NIDA and CPS were prevented by an NMDA antagonist or a neuronal nitric oxide synthase inhibitor. A nitric oxide scavenger or a soluble guanylate cyclase inhibitor prevented only the NIDA effects and the CPS effect was prevented by a non-selective antioxidant drug, as nitric oxide can also induce reactive oxygen species production. Our results suggest that CB1 and TRPV1 receptors in the ventromedial prefrontal cortex differently modulate the expression of conditioned emotional response through glutamatergic and nitrergic mechanisms, although different pathways may be involved.

Novel approaches for strengthening human fear extinction: The roles of novelty, additional USs, and additional GSs

Since Watson and Rayner's (1920) initial demonstration that human fear can be learned by means of Pavlovian conditioning, neuroscientific and behavioral studies have provided a thorough understanding of fear acquisition. Less is known about the manner in which we can harness insights from Pavlovian conditioning research to reduce fears and, most importantly, make the reduction of fear lasting and resistant against relapse. The current paper reviews three manipulations that have shown promise in achieving a reduction of conditional fear that is more resistant to relapse than is the reduction of conditional fear after standard extinction: novelty-facilitated extinction training, presentation of conditional-unconditional stimulus pairings or of unpaired unconditional stimuli during extinction, and extinction with additional stimuli that are similar to the original conditional stimuli. It summarizes past research involving human and non-human animal subjects and highlights knowledge gaps in the current literature. Moreover, it discusses potential mechanisms that mediate the reduction of fear seen as a result of these manipulations in an attempt to enhance our understanding of what renders fear extinction less vulnerable to the known pathways to fear relapse. It is hoped that this review will contribute to the achievement of the goal that was denied to Watson and Rayner, the development of experimental techniques that can be utilized to remove conditioned emotional responses permanently.

一例大学生失眠问题的元认知干预报告

文章介绍了对一例大学生失眠问题进行元认知技术干预的过程。女大学生C因对睡眠存在条件性焦虑情绪，进而产生不利于睡眠的思维和行为反应，最终形成潜意识状态下自动运行的失眠程序。咨询师运用元认知干预技术，高效干预来访者潜意识心理活动过程，解决失眠问题。一年后的回访结果表明心理干预效果明显、持久。 The article introduces the process of using Meta-cognitive intervention method to solve the college student's insomnia. The female college student had an anxiety about sleep, a kind of conditioned emotional response, and then her thinking and behavior responses are not conducive to sleep, eventually forming the subconscious state insomnia programs to run automatically. Consultant intervened the visitor's subconscious mental activity process and solved her insomnia by using Meta-cognitive intervention method. A year later, the return results showed that the effect of psychological intervention was obvious and persistent.

Sacred Maya incense, copal (Protium copal - Burseraceae), has antianxiety effects in animal models

Ethnopharmacological relevanceThe Maya have traditionally used copal, Protium copal, as incense during ceremonies since pre-Columbian times. Anecdotally, copal (when burned as incense), is thought to elicit mentally uplifting and calming effects. The main objective of this study was to determine whether the incense elicits anxiolytic-like behavior in animal models using rats. A second objective was to characterize active constituents and discern potential mechanism(s) of action, specifically the involvement of the GABAergic and endocannabinoid (eCB) systems. Despite the extensive Central American use of this resin, there are currently no known scientific behavioral or pharmacological studies done with the incense. Materials and methodsQuantification of the triterpenes in the copal resin and cold trapped incense was achieved by HPLC MS. Behavioral effects in rats were assessed using the elevated plus maze (EPM), social interaction (SI) test, conditioned emotion response (CER) and Novel object recognition (NOR) paradigms. Rats were exposed to burning copal (200 mg) over 5 min in a smoking chamber apparatus and then immediately tested in each behavioral paradigm. Follow-up SI tests were done using two antagonists flumazenil (1 mg/kg) and AM251 (1 mg/kg) administered systemically. Inhibition of MAGL (monoacylglycerol lipase) was measured by microplate assay with recombinant human enzyme and probe substrate. ResultsPhytochemical analysis revealed that copal resin and incense had high α- and β-amyrins and low lupeol triterpene content. Exposure to Protium copal incense significantly reduced anxiety-like behavior in the SI and CER tests. In contrast, no anxiolytic effects were observed in the EPM. The CER effect was time dependent. Both flumazenil and AM251 blocked the anxiolytic activity of copal revealing the involvement of GABAergic and endocannabinoid systems. Copal, as well as the identified triterpenes, potently inhibited monoacylglycerol lipase (MAGL) activity in vitro (IC50 ≤ 811 ng/mL). ConclusionsThis is the first study to show that copal incense from Protium copal elicits anxiolytic-like effects in fear and social interaction models as evidenced by a reduced learned fear behavior and an increase in active social interaction. It's high α and β-amyrin content suggests behavioral effects may be mediated, in part, by the known action of these terpenes at the benzodiazepine receptor. Furthermore, P. copal's observed activity through the eCB system via MAGL offers a new potential mechanism underlying the anxiolytic activity.

Metabolic activation of amygdala, lateral septum and accumbens circuits during food anticipatory behavior

When food is restricted to a brief fixed period every day, animals show an increase in temperature, corticosterone concentration and locomotor activity for 2–3h before feeding time, termed food anticipatory activity. Mechanisms and neuroanatomical circuits responsible for food anticipatory activity remain unclear, and may involve both oscillators and networks related to temporal conditioning. Rabbit pups are nursed once-a-day so they represent a natural model of circadian food anticipatory activity. Food anticipatory behavior in pups may be associated with neural circuits that temporally anticipate feeding, while the nursing event may produce consummatory effects. Therefore, we used New Zealand white rabbit pups entrained to circadian feeding to investigate the hypothesis that structures related to reward expectation and conditioned emotional responses would show a metabolic rhythm anticipatory of the nursing event, different from that shown by structures related to reward delivery. Quantitative cytochrome oxidase histochemistry was used to measure regional brain metabolic activity at eight different times during the day. We found that neural metabolism peaked before nursing, during food anticipatory behavior, in nuclei of the extended amygdala (basolateral, medial and central nuclei, bed nucleus of the stria terminalis), lateral septum and accumbens core. After pups were fed, however, maximal metabolic activity was expressed in the accumbens shell, caudate, putamen and cortical amygdala. Neural and behavioral activation persisted when animals were fasted by two cycles, at the time of expected nursing. These findings suggest that metabolic activation of amygdala-septal-accumbens circuits involved in temporal conditioning may contribute to food anticipatory activity.

Dorsal hippocampus cannabinoid type 1 receptors modulate the expression of contextual fear conditioning in rats: Involvement of local glutamatergic/nitrergic and GABAergic neurotransmissions

The cannabinoid receptor type 1 (CB1) is highly expressed in the dorsal portion of hippocampus – a brain region that has been involved in the control of conditioned emotional response (CER) in the contextual fear conditioning (CFC) model. These responses are characterized by increased freezing behavior and autonomic parameters. Moreover, CB1 receptors activation negatively modulate the release of several neurotransmitters, including glutamate and GABA, which also have been related to modulation of CER. Therefore, our aim was to investigate the involvement of CB1 receptors in the dorsal hippocampus on CER expression. Independent groups of male Wistar rats submitted to the contextual fear conditioning received bilateral intra-hippocampal injections (500 nL/side) of the following drugs or vehicle before re-exposure to the aversive context: AM251 (CB1 antagonist; 0.1, 0.3 and 1nmol); AP7 (NMDA antagonist; 1nmol)+AM251 (0.3nmol); NPLA (0.01nmol; nNOS inhibitor)+AM251 (0.3nmol); Bicuculline (1.3pmol; GABAA antagonist)+AM251 (0.1 and 1nmol). In the present paper, AM251 (0.3nmol) increased CER, while this response was prevented by both AP7 and NPLA pretreatment. After pretreatment with Bicuculline, the lower and higher ineffective doses of AM251 were able to increase the CER, supporting the balance between GABAergic and glutamatergic mechanisms controlling this response. Our results suggest that increased CER evoked by CB1 blockade in the dorsal hippocampus depends on NMDA receptor activation and NO formation. Moreover, a fine-tune control promoted by GABAergic and glutamatergic mechanisms in this brain area modulate the CER after CB1 blockade.

The dopamine D1 receptor agonist SKF81297 has dose-related effects on locomotor activity but is without effect in a CER trace conditioning procedure conducted with two versus four trials

In an appetitively motivated procedure, we have previously reported that systemic treatment with the dopamine (DA) D1 receptor agonist SKF81297 (0.4 and 0.8mg/kg) depressed acquisition at a 2s inter-stimulus-interval (ISI), suitable to detect trace conditioning impairment. However since DA is involved in reinforcement processes, the generality of effects across appetitively- and aversively-motivated trace conditioning procedures cannot be assumed. The present study tested the effects of SKF81297 (0.4 and 0.8mg/kg) in an established conditioned emotional response (CER) procedure. Trace-dependent conditioning was clearly shown in two experiments: while conditioning was relatively strong at a 3-s ISI, it was attenuated at a 30-s ISI. This was shown after two (Experiment 1) or four (Experiment 2) conditioning trials conducted in – as far as possible – the same CER procedure. Contrary to prediction, in neither experiment was there any indication that trace conditioning was attenuated by treatment with 0.4 or 0.8mg/kg SKF81297. In the same rats, locomotor activity was significantly enhanced at the 0.8mg/kg dose of SKF81297. These results suggest that procedural details of the trace conditioning variant in use are an important determinant of the profile of dopaminergic modulation.

Bed nucleus of the stria terminalis NMDA receptors and nitric oxide modulate contextual fear conditioning in rats

The bed nucleus of the stria terminalis (BNST) modulates anxiety-like responses, including conditioned emotional responses. Evidence suggests that glutamatergic neurotransmission in the BNST plays a role in the modulation of defensive responses. However, little is known about the involvement of glutamate NMDA receptor activation within the BNST, and its resultant increase in nitric oxide (NO) levels, in the expression of contextual fear conditioning (CFC). We investigated whether the antagonism of NMDA receptors or the reduction of NO levels in the BNST would attenuate behavioral and autonomic responses (i.e. increase in arterial pressure and heart rate, and decrease in tail cutaneous temperature) of rats submitted to a CFC paradigm. Intra-BNST infusion of AP7, an NMDA receptor antagonist, attenuated both behavioral and autonomic changes induced by CFC. Similar results were observed with NPLA and c-PTIO, an nNOS inhibitor and an NO scavenger, respectively. A positive correlation between BNST NO levels and the time spent in freezing behavior was also observed for animals submitted to the CFC. These findings indicate that the expression of CFC involves a facilitation of BNST NMDA receptor-NO signaling.This article is part of the Special Issue entitled ‘Ionotropic glutamate receptors’.

Anxiolytic activity and active principles of Piper amalago (Piperaceae), a medicinal plant used by the Q’eqchi’ Maya to treat susto, a culture-bound illness

Ethnopharmacological relevanceThe medicinal plant, Piper amalago L. (Piperaceae), is used traditionally by Q’eqchi’ Maya healers for the treatment of “susto” a culture-bound syndrome. Previous research suggests that susto symptoms may be a manifestation of anxiety. The objectives were to characterize the effect of ethanolic extract of P. amalago in behavioral assays of anxiety at doses representative of traditional use and to isolate active principles. Materials and methodsRats treated orally with low dose ethanolic extracts of P. amalago leaves (8–75mg/kg) were tested in several behavioral paradigms including the elevated plus maze (EPM), social interaction (SI), and conditioned emotional response (CER) tests, and compared to diazepam, a positive control. The active anxiolytic principle was isolated by bioassay guided isolation using an in vitro GABAA competitive binding assay. ResultsExtracts had significant anxiolytic activity in all behavioral tests, with the strongest activity in the SI and the CER paradigms. In an in vitro GABAA competitive binding assay, a 66.5µg/mL concentration of P. amalago ethanol extract displaced 50% of the GABAA–BZD receptor ligand [3H]-Flunitrazepam. Bioassay-guided fractionation identified a furofuran lignan, a molecule with structural similarity to yangambin, with high affinity for the GABAA-BZD receptor as the principle bioactive. ConclusionThe results suggest that the ethnobotanical use of this plant may have a pharmacological basis in its anxiolytic activity, as demonstrated in animal behaviour tests

Dorsolateral periaqueductal gray matter CB1 and TRPV1 receptors exert opposite modulation on expression of contextual fear conditioning

Cannabinoid type 1 (CB1) and Transient Potential Vanilloid type 1 (TRPV1) receptors in the dorsolateral periaqueductal gray (dlPAG) matter are involved in the modulation of conditioned response. Both CB1 and TRPV1 receptors are related to glutamate release and nitric oxide (NO) synthesis. It was previously demonstrated that both NMDA glutamate receptors and NO are involved in the conditioned emotional response. Therefore, one aim of this work was to verify whether dlPAG CB1 and TRPV1 receptors modulate the expression of contextual conditioned emotional response. Moreover, we also investigated the involvement of NMDA receptors and the NO pathway in this response. Male Wistar rats with local dlPAG guide cannula were submitted to contextual fear conditioning. Following 24 h, a polyethylene catheter was implanted in the femoral artery for cardiovascular recordings. After an additional 24 h, drugs were administered in the dlPAG and freezing behavior and autonomic responses were recorded during chamber re-exposure. Both a CB1 antagonist (AM251) and a TRPV1 agonist (Capsaicin; CPS) increased the expression of a conditioned emotional response. This response was prevented by an NMDA antagonist, a preferential neuronal NO synthase inhibitor, an NO scavenger and a soluble guanylate cyclase inhibitor (sGC). Furthermore, pretreatment with a TRPV1 antagonist also prevented the increased conditioned emotional response induced by AM251. Considering that GABA can counterbalance glutamate effects, we also investigated whether GABAA receptors were involved in the effect of a higher dose of AM251. Pretreatment with a GABAA receptor antagonist caused an increased conditioned emotional response by AM251. Our results support the possibility that dlPAG CB1 and TRPV1 receptors are involved in the expression of conditioned emotional response through the NMDA/NO/sGC pathway. Moreover, the opposite effects exerted by GABA and glutamate could produce different outcomes of drugs modulating eCBs.

Conditioned inhibition of emotional responses: Retardation and summation with cues for IAPS outcomes

Conditioned inhibition occurs when a stimulus inhibits the responses that would normally occur to a conditioned stimulus that previously predicted an outcome of interest (the unconditioned stimulus, which elicits responding unconditionally). The present study tested inhibitory learning using emotionally salient cues provided by the use of pictures from the International Affective Picture System (IAPS). The procedure in use was adapted to confirm the demonstration of conditioned inhibition using two key transfer tests, retardation and summation. Experiment 1 showed the development of the predicted discrimination learning for negative outcomes but not for positive outcomes. Experiment 2 found evidence for retardation. Furthermore, this reduced learning was clearly related to the conditioned emotional response to the US images; individuals rated transfer images as positive if they had previously signalled the absence of a negative outcome. Experiment 3 showed that the conditioned inhibition was by summation test. Thus, inhibitory learning was confirmed by both retardation and summation tests, which between them control for alternative explanations of apparent conditioned inhibition, conducted on different participants but using the same discrimination learning procedure. Moreover, the use of emotionally salient cues as the unconditioned stimuli more closely resembles the traditional Pavlovian paradigm.