Xigeng Zheng

Chinese Academy of Sciences | CAS

Fear relapse is a major challenge in the treatment of stress-related mental disorders. Most investigations have focused on fear return induced by stimuli associated with the initial fear learning, while little attention has been paid to fear return evoked after exposure to an unconditioned stressor. This study explored the neural mechanisms of fear...

Background Identifying neural substrates that are differentially affected by drugs of abuse and natural rewards is key to finding a target for an efficacious treatment for substance abuse. Melanin-concentrating hormone is a polypeptide with an inhibitory effect on the mesolimbic dopamine system. Here we test the hypothesis that melanin-concentratin...

Though the relationship between traumatic stress and social behavior, which has been explored for years, is dynamic and largely estimated between dyads, little is known about the causal effects of traumatic stress exposure on the time-dependent dynamic alterations in the social behaviors on a large-group level. We thus investigated the effect of a...

Background Negative affective states, e.g., anhedonia, may be linked to the long-lasting motivational processes associated with relapse. Here, this study investigated whether, and how, anhedonic states are influenced by stressful events that contribute to craving and relapse. Methods All male rats were pretreated with a binge-like morphine paradig...

The present protocol describes a novel conflict task as a model of inhibitory control in rats. In this model, a natural rewarding stimulus (sexual stimulus) that represents a high-value reward, and the aversive stimuli (pins), are concurrently presented. The male rats have to climb or jump over the obstacle full of pins to approach and investigate...

RationaleNegative affective states, e.g., anhedonia, are suggested to be involved in the long-lasting motivational processes associated with relapse. Here, we investigated whether anhedonic behaviors could be elicited by an acute stress after protracted abstinence from morphine. Objectives The behavioral responses to natural stimuli following expos...

Rationale: The negative affective state, e.g., anhedonia, emerges after abstinence from abused drugs may be linked to the motivational processes of drug craving and relapse. Although anhedonia diminishes over time with drug abstinence, it is not yet rather explicit whether anhedonia exists or not following protracted withdrawal. Objectives: The...

\textit{Rationale}$ Negative affective states, e.g., anhedonia, are suggested to be involved in the long-lasting motivational processes associated with relapse. Here, we investigated whether anhedonic behaviors could be elicited by an acute stress after protracted abstinence from morphine. $\textit{Objectives}$ The behavioral responses to natural s...

The return of learned fear is an important issue in anxiety disorder research since an analogous process may contribute to long-term fear maintenance or clinical relapse. A number of studies demonstrate that mPFC and hippocampus are important in the modulation of post-extinction re-expression of fear memory. However, the region-specific role of the...

The return of fear is an important issue in anxiety disorder research. Each time a fear memory is reactivated, it may further strengthen overactivation of the fear circuit, which may contribute to long-term maintenance of the fear memory. Recent evidence indicates that glucocorticoids may help attenuate pathological fear, but its role in the return...

Cognitive flexibility is a critical ability for adapting to an ever-changing environment in humans and animals. Deficits in cognitive flexibility are observed in most schizophrenia patients. Previous studies reported that the medial prefrontal cortex-to-ventral striatum and orbital frontal cortex-to-dorsal striatum circuits play important roles in...

Fear extinction decreases conditioned fear responses that normally occur when a conditioned stimulus (CS) is repeatedly presented in the absence of an aversive unconditioned stimulus (US), which is the behavioral basis of exposure therapy for posttraumatic stress disorder (PTSD). However, knowledge about the neurobiology of extinction is insufficie...

We used animal models of "forced swim stress" and "chronic unpredictable stress", and tried to reveal whether a passive coping style of high flotation behavior in forced swim stress predicts anhedonia behavior after chronic unpredictable stress, and whether the dopamine system regulates floating and anhedonia behaviors. Our results confirmed that d...

Exposure therapy is widely used to treat anxiety disorders, including posttraumatic stress disorder (PTSD). However, preventing the return of fear is still a major challenge after this behavioral treatment. An increasing number of studies suggests that high-dose glucocorticoid treatment immediately after trauma can alleviate the symptoms of PTSD in...

The anhedonia-like behaviors following about one-week withdrawal from morphine were examined in the present study. Male rats were pretreated with either a binge-like morphine paradigm or daily saline injection for 5 days. Three types of natural reward were used, food reward (2.5%, 4%, 15%, 30%, 40% and 60% sucrose solutions), social reward (male ra...

Accumulating evidence suggests that stress-dose corticosteroids impair fear memory in animals and humans. Corticosteroid treatment after critical illness is seen as a potential psychotropic medication by which to prevent posttraumatic stress disorder. However, individual difference in the responsiveness to stress (i.e., stress reactivity) is a fact...

Escalation of drug consumption is involved in the transition from drug use to addiction. Our previous study demonstrated that neuronal activation in ventral tegmental area (VTA) and substantia nigra (SN) was associated with behavioral sensitization induced by increasing doses of morphine. Here we sought to characterize the molecular mechanism under...

We have recently shown that post-extinction exposure of rats to a sub-conditioning procedure (SCP, i.e. retraining with a shock intensity that is too weak to induce by itself significant fear conditioning) or to acute stress provokes reemergence of extinguished fear. Furthermore, this SCP effect can be abolished by high-frequency stimulation (HFS)...

The negative affective state of opiate abstinence plays an important role in craving and relapse to compulsive drug use. The dopamine system participates in the reward effects of opiate use and the aversive effect of opiate abstinence. The amygdala is an essential neural substrate for associative learning of emotion. To establish a model of conditi...

Rationale The post-extinction exposure of rats to a sub-conditioning procedure (SCP; i.e., retraining with a shock intensity that is too weak to induce by itself significant fear conditioning) has been reported to provoke the reemergence of extinguished fear. This phenomenon can be prevented by chronic fluoxetine treatment. Objectives We sought to...

The transition to addiction often involves a gradual process of escalated drug intake. The purpose of the present study was to characterize neuronal activation in the ventral tegmental area (VTA) and substantia nigra (SN) following chronic escalating-dose morphine exposure (days 1-7, 2 mg/kg/d; days 8-21, beginning at 10 mg/kg/d, increasing by 2 mg...

The activity of hypothalamic-pituitary-adrenal (HPA) axis is paralleled with the behavioral disturbances of individuals with high anxiety and has been conceptualized to involve a fear conditioning process. We investigated the effect of modulating HPA axis activity on fear conditioning for high (HA) and low (LA) anxiety individuals. Firstly, male Sp...

Drug seeking, craving, and relapse can be triggered by environmental stimuli that acquire motivational salience through repeated associations with the drug's effects. Previous studies indicated that the dopamine D(3) receptor (Drd3) might be involved in the expression of drug-conditioned responses in rats, and brain-derived neurotrophic factor (BDN...

The nucleus accumbens (NAc) is involved in contextual drug associations, which might be particularly important for environmental cue-induced relapse to drug seeking. In the present study, rats were first administered repeated morphine for 5 days (5 mg/kg, i.p.) in a contextually paired and unpaired design. After reexposure to the morphine-associate...

Both conditioned responses (CRs) and sensitized behaviors induced by addictive drugs are considered to reflect drug-seeking motivation. Based on an excitatory conditioning model of behavioral sensitization, this work hypothesizes that conditioned locomotor activity and locomotor sensitization concomitantly occur using different drug treatment regim...

BACKGROUND: Drug-associated conditioned stimuli are a key factor to induce morphine relapse. To date, limited evidence is available regarding the impact of drug history on propensity or vulnerability to relapse after long-term abstinence. OBJECTIVE: To determine the effect of morphine pre-exposure on acquisition, maintenance and reinstatement of mo...

Previous research demonstrated excessive decreases in reward sensitivity and increases in harm avoidance in depressed individuals. These results straightly lead to a hypothesis that depressed patients should avoid novelty or express reduced novelty-seeking behavior. Nevertheless, literature in this regard is inconsistent. Furthermore, whether the p...

Orexins are neuropeptides involved in multiple neurophysiological functions such as reward and motivation. However, it is not clear whether orexins are implicated in sexual motivation. This study aims to evaluate the effects of orexin A and the OX(1)R antagonist SB334867 on unconditioned sexual motivation. Forty-five male Wistar rats are divided in...

Behavioural studies have provided strong evidence for common substrates in the rewards of natural and addictive substances, but it is still unclear whether there is a common glutamatergic NMDA receptor mechanism involved in the processing of reward for both. The present study was designed to investigate the effects of MK-801 (0.1mg/kg) on the expre...

Large individual differences have been identified toward varied addictive effects as evidenced in self-administration, place conditioning, and psychomotor stimulation paradigms, which have been primarily attributed to the role of congenital factors. However, it remains unknown whether environmental factors, like extraneous social stress events, cou...

The hippocampus, being sensitive to stress and glucocorticoids, plays significant roles in certain types of learning and memory. Therefore, the hippocampus is probably involved in the increasing drug use, drug seeking, and relapse caused by stress. We have studied the effect of stress with morphine on synaptic plasticity in the CA1 region of the hi...

The relationship between motor responses in a novel environment and susceptibility to place conditioning effect of psychostimulants has been reported in adult rats. However, it is in question whether this correlation could be generalized to motor activity in rats of juvenile period and place conditioning effect in their adulthood for narcotic morph...

Previous studies demonstrated that the rewarding effect of psychostimulants, such as amphetamine and cocaine, can be predicted by locomotor activity toward novelty in a free-choice situation but not motor response developed in inescapable environment. However, whether this relationship also exists with narcotic morphine remains unclear. In the pres...

To investigate effects of morphine on acquisition process of rats a nd interactions of opioid and cholinergic systems by Morris water maze performance. Morris water maze was used to measure the latency of rats with drug s treatment to find the covert platform. Chronic morphine administration (10 mg/kg) impaired the acquisition process of rats in Mo...