Therapeutic sleep deprivation for major depressive disorder: A randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is treated primarily using antidepressant drugs, but clinical effects may be delayed for weeks to months. This study investigated the efficacy of brief therapeutic sleep deprivation (TSD) for inducing rapid improvements in MDD symptoms. METHODS: From November 2020 to February 2023, 54 inpatients with MDD were randomly allocated to TSD and Control groups. The TSD group (23 cases) remained awake for 36 h, while the Control group (31 cases) maintained regular sleep patterns. All participants continued regular drug therapy. Mood was assessed using the 24-item Hamilton Depression Scale (HAMD-24) at baseline and post-intervention in both groups. In the TSD group, the Visual Analogue Scale (VAS) was utilized to evaluate subjective mood during and after the intervention. Cognitive function was assessed at baseline and post-intervention using the Montreal Cognitive Assessment (MoCA). Objective sleep parameters were recorded in the TSD group by polysomnography. The follow-up period spanned one week. RESULTS: HAMD-24 scores did not differ between groups at baseline or post-intervention. However, the clinical response rate was 34.8 % higher in the TSD group on day 3 post-intervention compared to the Control group (3.2 %), but not sustained by day 7. Moreover, responders demonstrated a faster improvement in the VAS score during TSD than non-responders (p = 0.047). There were no significant differences in MoCA scores or objective sleep parameters between the groups. LIMITATIONS: Small sample size and notable attrition rate. CONCLUSIONS: Therapeutic sleep deprivation can rapidly improve MDD symptoms without influencing sleep parameters or cognitive functions. Assessment of longer-term effects and identification of factors predictive of TSD response are warranted.

Dual Proton/Silver-Catalyzed Serial (5 + 2)-Cycloaddition and Nazarov Cyclization of (E)-2-Arylidene-3-hydroxyindanones with Conjugated Eneynes: Synthesis of Indanone-Fused Benzo[cd]azulenes.

A one-pot step-economic tandem process involving (5 + 2)-cycloaddition and Nazarov cyclization reactions has been reported for the facile synthesis of indanone-fused benzo[cd]azulenes from (E)-2-arylidene-3-hydroxyindanones and conjugated eneynes. This highly regio- and stereoselective bisannulation reaction is enabled by dual silver and Brønsted acid catalysis and opens up a new avenue for the construction of important bicyclo[5.3.0]decane skeletons.

[Effects of butylphthalide on H2S/CBS pathway in hippocampal and amygdala and learning and memory ability in chronic alcoholism rats].

Objective: To investigate the effects of butylphthalide (NBP) on learning and memory related ability, hydrogen sulfide (H2S) content in hippocampus and amygdala, cystathionine-ß-synthase (CBS) expression and mitochondrial ATPase activity in rats with chronic alcoholism. Methods: Ninety SD male rats were randomly divided into three groups: normal control group (NC), model group (M) and butylphthalide remedy group (BR). Except for the control group, the water solution containing 6% (v/v) alcohol was used as the sole source of drinking water in the other two groups. After 14 days of feeding, the butylphthalide remedy group was injected with NBP intraperitoneally at the dose of 5 mg/kg once a day for 14 consecutive days, and the remaining two groups were injected with the same dose of normal saline. The control group subsequently used the Morris water maze method to observe and record the animals after entering the water. The time required for the underwater platform, their strategies and their swimming trajectories could analyze and infer the animal's ability to learn and remember. H2S concentration, CBS expression and mitochondrial ATPase activity in hippocampus and amygdale were dectected. Results: Compared with NC group, the latency period and swimming distance of M group were increased, the content of H2S and the mean optical density of CBS in hippocampus and amygdala were increased, and the activity of mitochondrial ATPase in hippocampus and amygdala was decreased significantly (P＜0. 01) . Compared with the M group, the latency period and swimming distance of learning and memory performance of BR group were decreased, the content of H2S and the mean optical density of CBS in hippocampus and amygdala were decreased, and the activity of mitochondrial ATPase in hippocampus and amygdala was increased significantly (P＜0. 01) . Conclusion: NBP can alleviate the effect of ethanol on learning and memory in rats, which may be related to the effect of NBP on the concentration of H2S and the expression of CBS in the amygdala of hippocampus and the increase of ATPase activity.

Inhibition of naltrexone on relapse in methamphetamine self-administration and conditioned place preference in rats.

Methamphetamine (METH) addiction has been widely spread and caused severe problems both in society and public health in recent years, but there is a shortage of medication available. The naltrexone (NTX) as a non-selective opioid receptor antagonist has been widely applied to treat alcohol addiction and the relapse to opioid addiction after detoxification. In the present study, we investigated the potent pharmacotherapeutic effect of NTX in attenuating relapse to drug-seeking behavior in the METH self-administration and conditioned place preference (CPP) in rats. The results showed that acute intragastrical administration of NTX (40 mg/kg) significantly reduced cue-induced drug-seeking behavior after extinction training. The similar inhibition effect was observed in the CPP model, that the intragastrical administration of NTX (30 mg/kg) significantly disrupted the reactivation induced by intraperitoneal injection of METH (0.5 mg/kg) after the extinction training process. However, respective intragastrical administration of NTX (20 or 40 mg/kg) failed to alter the dose-response curve of METH under fixed ratio 2 program and intraperitoneal injection of METH (1.0 mg/kg)-induced reinstatement in rats self-administration. Overall, our findings suggest that NTX has the pharmacotherapeutic potential in reducing the relapse of METH addiction, which deserves further investigation as a promising medication for the treatment of METH addiction.

Chronic stress increases pain sensitivity via activation of the rACC-BLA pathway in rats.

Exposure to chronic stress can produce maladaptive neurobiological changes in pathways associated with pain processing, which may cause stress-induced hyperalgesia (SIH). However, the underlying mechanisms still remain largely unknown. In previous studies, we have reported that the amygdala is involved in chronic forced swim (FS) stress-induced depressive-like behaviors and the exacerbation of neuropathic pain in rats, of which, the basolateral amygdala (BLA) and the central nucleus of the amygdala (CeA) are shown to play important roles in the integration of affective and sensory information including nociception. Here, using in vivo multichannel recording from rostal anterior cingulate cortex (rACC) and BLA, we found that chronic FS stress (CFSS) could increase the pain sensitivity of rats in response to low intensity innoxious stimuli (LIS) and high intensity noxious stimuli (HNS) imposed upon the hindpaw, validating the occurrence of SIH in stressed rats. Moreover, we discovered that CFSS not only induced an increased activity of rACC neuronal population but also produced an augmented field potential power (FPP) of rACC local field potential (LFP), especially in low frequency theta band as well as in high frequency low gamma band ranges, both at the baseline state and under LIS and HNS conditions. In addition, by using a cross-correlation method and a partial directed coherence (PDC) algorithm to analyze the LFP oscillating activity in rACC and BLA, we demonstrated that CFSS could substantially promote the synchronization between rACC and BLA regions, and also enhanced the neural information flow from rACC to BLA. We conclude that exposure of chronic FS stress to rats could result in an increased activity of rACC neuronal population and promote the functional connectivity and the synchronization between rACC and BLA regions, and also enhance the pain-related neural information flow from rACC to BLA, which likely underlie the pathogenesis of SIH.

Association between sleep duration during pregnancy and gestational diabetes mellitus: a meta-analysis.

OBJECTIVE: Sleep is critical for glucose metabolism. Pregnant women often have sleep disturbances and extreme sleep duration. Investigations of the relationship between sleep duration during pregnancy and gestational diabetes mellitus (GDM) have reported inconsistent results. The present study aimed to meta-analyze the relationship between sleep duration during pregnancy and GDM risk. METHODS: We performed a systematic search of the PubMed, ISI Web of Science, and PsycINFO databases for studies that were published up to October 2017, that reported associations between sleep duration during pregnancy and GDM risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated as the effect sizes for all studies. Heterogeneity and potential publication biases were assessed. RESULTS: A total of 4366 papers were retrieved, among which seven studies assessed the relationship between sleep duration during pregnancy and GDM development. The seven articles included 18,203 subjects at baseline and 1294 GDM cases during follow-up. Compared to normal sleep duration, extreme sleep duration during early and middle pregnant stages had a close relationship with GDM based upon pooled data from prospective and cross-sectional studies. Prospective results showed that long sleep duration during pregnancy was a risk factor for GDM, but not short sleep duration. Publication biases were found when analyzing the relationship between extreme sleep duration and GDM. CONCLUSIONS: Extreme sleep duration during pregnancy is closely associated with GDM. Moreover, long but not short sleep duration can predict the risk of developing GDM. These findings remind us of the importance of sleep duration control during pregnancy and help optimize early strategies for the prevention of GDM.

Unveiling excited state energy transfer and charge transfer in a host/guest coordination cage.

Host-guest charge transfer (HGCT) plays a key role in applications from solar energy conversion to photocatalysis. Herein, a HGCT system, a pillared Pt(ii) metallacage with encapsulated coronene was synthesized and the ultrafast excited-state dynamics were investigated by combination of femtosecond transient absorption spectroscopy, nanosecond transient emission spectrocopy and quantum chemistry calculations. Two significant ultrafast dynamic processes were unveiled: (i) charge transfer from a singlet local excited (1LE) state associated with the coronene moiety to a 1HGCT state with τ = 9.5 ps; and (ii) triplet-triplet energy transfer from a high 3HGCT state to a 3LE state with τ = 139.5 ps. The resulting long-lived species, the lowest 3LE and 3HGCT states eventually decay to the ground state in microsecond time scales of 5.2 and 43.4 µs respectively. Moreover, a clear mechanism depicting the main excited-state decay pathways connecting the initial photoexcited transients with the resulting species was proposed.

Efficacy and Acceptability of Cariprazine in Acute Exacerbation of Schizophrenia: Meta-Analysis of Randomized Placebo-Controlled Trials.

PURPOSE: The purpose of this study was to assess the efficacy and acceptability of cariprazine treatment in acute exacerbation of schizophrenia. METHODS: This review included randomized controlled trials of patients with acute exacerbation of schizophrenia in relation to efficacy and acceptability. The efficacy outcomes were assessed by pooling standardized mean differences (SMDs) calculated from the difference in the reduction in the mean of the Positive and Negative Syndrome Scale (PANSS) total score, PANSS positive and negative scores, and response rate. The primary acceptability outcomes were determined by pooling the risk ratios (RRs) of discontinuation for any reason, the incidence of serious adverse events, and treatment emergent events. FINDINGS: Four randomized controlled trials consisting of 1843 patients met all inclusion and exclusion criteria. Efficacy analysis showed significant positive effects in relation to cariprazine therapy (SMD: -0.37, P < 0.00001 for PANSS total score change; SMD: -0.32, P < 0.00001 for PANSS positive score change; SMD: -0.32, P < 0.0001 for PANSS negative score change; RR, 1.41; 95% confidence interval [CI], 1.19-1.67; P < 0.0001 for response rate). For primary acceptability outcomes, less patients taking cariprazine discontinued treatment for any reason compared with patients receiving placebo (RR, 0.90; 95% CI, 0.78-1.04; P = 0.16). Significantly less patients on cariprazine had serious adverse events during the double-blind treatment period compared with patients taking placebo (RR, 0.55; 95% CI, 0.34-0.89; P = 0.01). Significantly more patients on cariprazine had treatment emergent events compared with those receiving placebo (RR, 1.10; 95% CI, 1.03-1.18; P = 0.006). IMPLICATIONS: Results suggest that cariprazine may be an effective and acceptable treatment for schizophrenia and future research is warranted.

[Effects of aminooxyacetic acid on the learning and memory ability and its possible mechanism in rats with chronic alcoholism].

OBJECTIVE: To investigate the effects of aminooxyacetic acid (AOAA) on learning and memory ability and possible mechanisms in rats with chronic alcoholism. METHODS: Sixty SD male rats were randomly divided into three groups on average.The model group rats and the remedy group rats were fed with the water containing (v/v) 6% alcohol for 28 days.After 14 days, the remedy group rats were treated with AOAA (5 mg/kg·d) by intraperitoneal injection once a day for 14 days and the other two group rats were treated with the equal amount of saline by intraperitoneal injection every day.Five days before the end of the experiment, the water maze test was carried out to test the learning and memory ability of rats for 5 days.Subsequently, the content of H2S, the activity of ATP enzyme and the expression of 5-HT in hippocampus were measured. RESULTS: Compared with the rats in the control group, the latency and the swimming distance of the 2nd to the 4th day, the content of H2S in hippocampus of rats in the model group were all increased, the mitochondrial ATP enzyme activity in hippocampus and the positive expression of 5-HT in hippocampus CA1 and CA3 of rats in the model group were decreased (P<0.01).Compared with the rats in the model group, the latency and the swimming distance of the 2nd to the 4th day, the content of H2S in hippocampus of the rats in the remedy group were decreased, the mitochondrial ATP enzyme activity in hippocampus and the positive expression of 5-HT in hippocampus CA1 and CA3 of rats in the model group were increased (P<0.01). CONCLUSIONS: AOAA could alleviate the symptoms of chronic alcoholism rats, which may be related to the effects of AOAA on the content of H2S, the mitochondrial enzyme activity and the expression of 5-HT in hippocampus.

Intraligand Charge Transfer Sensitization on Self-Assembled Europium Tetrahedral Cage Leads to Dual-Selective Luminescent Sensing toward Anion and Cation.

Luminescent supramolecular lanthanide edifices have many potential applications in biology, environments, and materials science. However, it is still a big challenge to improve the luminescent performance of multinuclear lanthanide assemblies in contrast to their mononuclear counterparts. Herein, we demonstrate that combination of intraligand charge transfer (ILCT) sensitization and coordination-driven self-assembly gives birth to bright EuIII tetrahedral cages with a record emission quantum yield of 23.1%. The ILCT sensitization mechanism has been unambiguously confirmed by both time-dependent density functional theory calculation and femtosecond transient absorption studies. Meanwhile, dual-responsive sensing toward both anions and cations has been demonstrated making use of the ILCT transition on the ligand. Without introduction of additional recognition units, high sensitivity and selectivity are revealed for the cage in both turn-off luminescent sensing toward I- and turn-on sensing toward Cu2+. This study offers important design principles for the future development of luminescent lanthanide molecular materials.

An efficient ratiometric fluorescence sensor based on metal-organic frameworks and quantum dots for highly selective detection of 6-mercaptopurine.

The development of a simple and accurate quantitative method for the determination of 6-mercaptopurine (6-MP) is of great importance because of its serious side effects. Ratiometric fluorescence (RF) sensors are not subject to interference from environmental factors, and exhibit enhanced precision and accuracy. Therefore, a novel RF sensor for the selective detection of 6-MP was developed based on a dual-emission nanosensor. The nanosensor was fabricated by combining a blue-emission metal-organic framework (MOF) NH2-MIL-53(Al) (λem=425nm) with green-emission 3-mercaptopropionic acid-capped CdTe quantum dots (MPA-CdTe QDs) (λem=528nm) under a single excitation wavelength (335nm). Upon addition of 6-MP, the fluorescence of NH2-MIL-53(Al) in the nanohybrid was selectively quenched due to strong inner filter effects, while the fluorescence of the MPA-CdTe QDs was enhanced. The novel RF sensor exhibited higher selectivity towards 6-MP than CdTe QDs alone, and higher sensitivity than MOFs alone. 6-MP could be detected in the range of 0-50µM with a detection limit of 0.15µM (S/N=3). The developed sensor was applied for the determination of 6-MP in human urine samples and satisfactory results were obtained. Overall, a novel and efficient fluorescence-based method was developed for the detection of 6-MP in biosamples.

The association of HTR3A mRNA expression and craving in Han Chinese alcohol-dependent patients: a preliminary study.

BACKGROUND: 5-Hydroxytryptamine (5-HT) 3 receptor plays a crucial role in craving of alcohol dependence. Recent evidence shows that chronic alcohol exposure causes changes in gene expression and induces behavioral changes. However, the relationship between gene expression of 5-HT3 receptor and craving in alcohol-dependent patients is not fully understood. OBJECTIVES: The aim of this preliminary study was to investigate the relationship between gene expression of the 5-HT3 receptor and craving in alcohol-dependent patients and the epigenetic mechanism. METHODS: We recruited 50 male Han Chinese alcohol-dependent patients and 46 male Han Chinese healthy controls. We investigated the changes of HTR3A mRNA, which encodes the 5-HT3 receptor A subunit, and H3K9 acetylation in HTR3A promoter region. Obsessive Compulsive Drinking Scale (OCDS) was used to assess the craving of alcohol-dependent patients relative to controls. RESULTS: HTR3A mRNA expression levels and acetylation levels of H3K9 in the HTR3A promoter region were significantly higher in the alcohol-dependent patients. HTR3A mRNA expression levels were positively correlated with OCDS scores. Moreover, HTR3A mRNA expression levels were positively correlated with acetylation levels of H3K9 in HTR3A promoter region. CONCLUSION: The current findings suggest that HTR3A mRNA expression levels were positively correlated with craving in Han Chinese alcohol-dependent patients. The regulation of H3K9 histone acetylation in HTR3A promoter region may offer a target for the treatment of alcohol dependence.

Effect of the Hydrogen Bond on Photochemical Synthesis of Silver Nanoparticles.

The effect of a hydrogen bond on the photochemical synthesis of silver nanoparticles has been investigated via experimental and theoretical methods. In a benzophenone system, the photochemical synthesis process includes two steps, which are that hydrogen abstraction reaction and the following reduction reaction. We found that for the first step, an intermolecular hydrogen bond enhances the proton transfer. The efficiency of hydrogen abstraction increases with the hydrogen bond strength. For the second step, the hydrogen-bonded ketyl radical complex shows higher reducibility than the ketyl radical. The inductively coupled plasma-optical emission spectroscopy (ICP-OES) measurement exhibits a 2.49 times higher yield of silver nanoparticles in the hydrogen bond ketyl radical complex system than that for the ketyl radical system. Theoretical calculations show that the hydrogen bond accelerates electron transfer from the ketyl radical to the silver ion by raising the SOMO energy of the ketyl radical; thus, the SOMO-LUMO interaction is more favorable.

[Effects of polydatin on learning and memory and Cdk5 kinase activity in the hippocampus of rats with chronic alcoholism].

OBJECTIVE: To observe the effects of polydatin on learning and memory and cyclin-dependent kinase 5 (Cdk5) kinase activity in the hippocampus of rats with chronic alcoholism. METHODS: Forty rats were randomly divided into 4 groups: control group, chronic alcoholism group, low and high polydatin group. The rat chronic alcoholism model was established by ethanol 3.0 g/(kg · d) (intragastric administration). The abstinence scoring was used to evaluate the rats withdrawal symptoms; cognitive function was measured by Morris water maze experiment; Cdk5 protein expression in the hippocampus was detected by immunofluorescence; Cdk5 kinase activity in the hippocampus was detected by liquid scintillation counting method. RESULTS: The abstinence score, escape latency, Cdk5 kinase activity in chronic alcoholism group rats were significantly higher than those of control group (P < 0.05). The abstinence score, escape latency in high polydatin group rats were significantly lower than those of chronic alcoholism group (P < 0.05); Cdk5 kinase activity in high and low polydatin group rats was significantly lower than that of chronic alcoholism group( P < 0.05); immunofluorescence showed that the Cdk5 positive cells of chronic alcoholism group were significantly increased compared with control group (P < 0.05), and the Cdk5 positive cells of polydatin groups were significantly decreased compared with chronic alcoholism group ( P < 0.05). CONCLUSION: Polydatin-reduced the chronic alcoholism damage may interrelate with regulation of Cdk5 kinase activity.

Quetiapine mitigates the ethanol-induced oxidative stress in brain tissue, but not in the liver, of the rat.

Quetiapine, an atypical antipsychotic, has been employed to treat alcoholic patients with comorbid psychopathology. It was shown to scavenge hydroxyl radicals and to protect cultured cells from noxious effects of oxidative stress, a pathophysiological mechanism involved in the toxicity of alcohol. This study compared the redox status of the liver and the brain regions of prefrontal cortex, hippocampus, and cerebellum of rats treated with or without ethanol and quetiapine. Ethanol administration for 1 week induced oxidative stress in the liver and decreased the activity of glutathione peroxidase and total antioxidant capacity (TAC) there. Coadministration of quetiapine did not protect glutathione peroxidase and TAC in the liver against the noxious effect of ethanol, thus was unable to mitigate the ethanol-induced oxidative stress there. The ethanol-induced alteration in the redox status in the prefrontal cortex is mild, whereas the hippocampus and cerebellum are more susceptible to ethanol intoxication. For all the examined brain regions, coadministration of quetiapine exerted effective protection on the antioxidants catalase and total superoxide dismutase and on the TAC, thus completely blocking the ethanol-induced oxidative stress in these brain regions. These protective effects may explain the clinical observations that quetiapine reduced psychiatric symptoms intensity and maintained a good level of tolerability in chronic alcoholism with comorbid psychopathology.

Security of quantum digital signatures for classical messages.

Quantum digital signatures can be used to authenticate classical messages in an information-theoretically secure way. Previously, a novel quantum digital signature for classical messages has been proposed and gave an experimental demonstration of distributing quantum digital signatures from one sender to two receivers. Some improvement versions were subsequently presented, which made it more feasible with present technology. These proposals for quantum digital signatures are basic building blocks which only deal with the problem of sending single bit messages while no-forging and non-repudiation are guaranteed. For a multi-bit message, it is only mentioned that the basic building blocks must be iterated, but the iteration of the basic building block still does not suffice to define the entire protocol. In this paper, we show that it is necessary to define the entire protocol because some attacks will arise if these building blocks are used in a naive way of iteration. Therefore, we give a way of defining an entire protocol to deal with the problem of sending multi-bit messages based on the basic building blocks and analyse its security.

Outer membrane vesicles isolated from two clinical Acinetobacter baumannii strains exhibit different toxicity and proteome characteristics.

Outer membrane vesicles (OMVs) are well-characterized virulence factors produced by Gram-negative bacteria. Here, we isolated two clinical Acinetobacter baumannii strains, the multidrug-resistant A. baumannii (MDRAb) A38 and non-MDRAb 5806. Strain A38 produced more abundant OMVs than strain 5806 when cultured to the early stationary phase. The results from cell proliferation assays and real-time PCR analyses indicated that A38 OMVs induced more powerful cytotoxicity and stronger innate immune responses compared with 5806 OMVs. Moreover, SDS-PAGE and LC-MS/MS analyses revealed that A38 OMVs contained more virulence factors, including Omp38, EpsA, Ptk, GroEL, hemagglutinin-like protein, and FilF. Taken together, the results of the present study suggest that MDRAb might produce abundant OMVs with more virulent factors facilitating the worse outcome, a finding that merits further study.

The presence of genogroup II norovirus in retail shellfish from seven coastal cities in China.

Noroviruses (NoVs) are commonly occurring pathogens that cause gastroenteritis. Outbreaks of viral diseases have often been ascribed to the consumption of contaminated shellfish. Our objective was to evaluate the presence and contamination levels of NoV in shellfish sold at seafood markets in China. We tested 840 shellfish samples (Crassostrea gigas, Mytilus edulis, Azumapecten farreri, SinoNoVacula constricta, Scapharca subcrenata, Ruditapes philippinarum) that were collected from seven cities around the Yellow and Bohai Seas in China between December 2009 and November 2011. We used real-time RT-PCR to detect NoV in purified concentrates from the stomach and digestive diverticula of these shellfish. NoV was detected in 19.35 % (N = 155), 16.67 % (N = 114), 5.70 % (N = 158), 8.82 % (N = 136), 13.74 % (N = 131), and 16.44 % (N = 146) of oyster, mussel, scallop, razor clam, ark shell, and clam samples, respectively. The average detection rate was 13.33 % (112/840). Nucleotide sequencing of the NoV RT-PCR products demonstrated that all strains belonged to NoV genotype GII.12, except two that belonged to GI.3. More than 10² copies of the NoV genome were detected in 69 of 112 positive shellfish samples. Our results suggest that ~13 % of shellfish harbor NoV, and GII.12 NoV is the primary strain in shellfish purchased at markets in seven coastal cities in China.

[Changes of protein kinase A expressions in central amygdaloid nuclei during the process of chronic morphine-induced conditioned place aversion in rats].

OBJECTIVE: To explore neurobiological mechanisms of the withdrawal-induced aversion. The changes of protein kinase A were measured in central amygdaloid nucleic (CeA) of conditioned place aversion (CPA) model rats. METHODS: (1) All 72 male SD rats were divided into three groups, model group (MN group), and control group (MS group and SN group). MN group was injected with morphine,6.5 days, 10 mg/kg, intraperitoneally (ip), twice per day, naloxone injection, 0.3 mg/kg, ip, along with conditioned place aversion training, to develop the CPA model. The MS group was administrated equivalent volume of morphine and saline. Also the SN group was injected with equivalent volume of saline and naloxone. (2) During the process of morphine-induced CPA, the expression of protein kinase A was assayed with immunohistochemistry in the CeA. RESULTS: In the MN group, protein kinase A expressions in the CeA occurred adaptive changes at different points of CPA (P < 0.05). Protein kinase A expressions after establishment(Day7,134.43 +/- 4.481, P < 0.05), and after extinction (Day 13, 141.01 +/- 3.360, P < 0.01), and after reinstatement (Day 14,137.18 +/- 40.330, P < 0.05) were also lower than those before the establishment of the CPA (Day 5, 124.48 +/- 6.722). However, PKA expressions were not significantly different both in MS group (P > 0.05)and SN group (P > 0.05). CONCLUSION: (1) Protein kinase A expression, in turn regulating the aversion expression, in the CeA probably is a key pathway contributing to the development of CPA. (2) The neuroadaptation mediated by protein kinase A may be one of the important molecular underpinnings of CPA.