Animals ; Conditioning, Classical ; Evoked Potentials, Somatosensory ; Fear ; psychology ; Male ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological

Previous studies have indicated phase-related differences in conditioned acquisition and extinction. In recent years, many researchers used event-related potential (ERP) technology to assess the extent of the acquisition and extinction. Therefore, this study was aimed to assess the sex- and menstrual cycle-dependent effects on the conditioned acquisition and extinction using ERP technology. Thirty-two females at two phases (menses phase, FM, and luteal phase, FL) of their menstrual cycle and 16 males participated in the experiment. The experiment consisted of two stages: acquisition stage and extinction stage. In the acquisition stage, in the predictable context, a condition stimulus (CS) was always followed by the presentation of a negative picture or a neutral picture; but in the unpredictable context, a CS was paired with a negative picture or a neutral picture 20% of the time. In the extinction stage, only CS was presented. The results showed that at acquisition stage, significant larger P2 amplitudes were recorded in female subjects in FL and FM in comparison with those of males. The female subjects in FL may acquire the strongest CS-US conditional connection. At extinction stage, the female subjects in FL showed larger P2 amplitudes than males, but there were no significant differences in P2 amplitudes between the males and females in FM. The results suggest that the females in FL allocate more attention resources to the acquisition of a conditioned response and delayed extinction. In conclusion, we suggest that female menstrual cycle may modulate conditioned acquisition and extinction processes, and our ERP data may provide an explanation for the premenstrual dysphoric disorder.
Attention ; Conditioning, Classical ; Evoked Potentials ; Extinction, Psychological ; Female ; Humans ; Male ; Menstrual Cycle ; Sex Factors

OBJECTIVE: To analyze the relationship between the electroencephalograph (EEG) changes of temporal association cortex (TeA) and the drug-seeking behavior in heroin-induced conditioned place preference (CPP) rats. METHODS: The rats were randomly divided into an operated control group and a heroin-induced CPP group after the electrodes were buried in TeA by stereotactic technology. The TeA EEG was recorded by the CPP video system combining with the EEG wireless telemetry, where the rats stayed in black or white chambers, shuttling from black to white chambers or from white to black chambers. RESULTS: Compared with the operated control group, the percentage of TeA θ waves was increased significantly when staying in black or white chambers in the heroin-induced CPP group (P<0.05, P<0.01). Compared with the operated control group, when rats shuttling between the 2 chambers, the TeA δ waves were reduced (P<0.01), but β waves, β2 waves in particular, were increased (P<0.01) in the heroin-induced CPP group (P<0.05, P<0.01). Compared with staying in the black chamber, when heroin-induced CPP rats were shuttling between black and white chambers, the right TeA θ waves were reduced, and β waves, β2 waves in particular, were increased (P<0.01). Compared staying in the white chamber with shuttling between white and black chambers in the heroin induced CPP rats, the right TeA θ waves, but not β waves, were reduced (P<0.01). CONCLUSION The EGG changes on the right TeA in the heroin-induced CPP rats, including the increased fast waves (β, β2) and the reduced slow wave (θ), may be related to drug-seeking behaviors.
Animals ; Conditioning, Psychological ; drug effects ; Drug-Seeking Behavior ; Electroencephalography ; Heroin ; Rats ; Telemetry ; Temporal Lobe ; drug effects

Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.
Animals ; Brain ; Cocaine ; Conditioning, Operant ; Extinction, Psychological ; Lipidomics ; Male ; Mice ; Simvastatin/therapeutic use*

Animals ; Apoptosis ; Hippocampus ; pathology ; Male ; Neurons ; pathology ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological ; pathology

OBJECTIVETo 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.

RESULTSIn 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.

Amygdala ; enzymology ; Animals ; Conditioning, Operant ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; Disease Models, Animal ; Extinction, Psychological ; Male ; Morphine Dependence ; psychology ; Rats ; Rats, Sprague-Dawley

Animals ; Conditioning (Psychology) ; drug effects ; Extinction, Psychological ; drug effects ; physiology ; Fear ; drug effects ; physiology ; Male ; Mifepristone ; pharmacology ; Rats ; Rats, Sprague-Dawley

Conditioned fear and its abnormal extinction are involved in the psychopathology of anxiety disorders, such as posttraumatic stress disorder (PTSD). Cognitive enhancing agents have been demonstrated to alter fear extinction in many animal research literatures. The present review has examined the pharmacological role of gamma-aminobutyric acid (GABA), glutamatergic, cholinergic, adrenergic, dopaminergic, and cannabinoid as well as compounds able to alter the epigenetic and neurotrophic mechanism in fear extinction, highlighting great hope for the future treatment of anxiety disorders with new agents based on the fear extinction.
Animals ; Anxiety Disorders ; drug therapy ; psychology ; Cannabinoids ; pharmacology ; therapeutic use ; Conditioning, Psychological ; drug effects ; Extinction, Psychological ; drug effects ; Fear ; drug effects ; psychology ; Humans ; Nootropic Agents ; pharmacology ; Stress Disorders, Post-Traumatic ; drug therapy ; psychology ; gamma-Aminobutyric Acid ; pharmacology ; therapeutic use

OBJECTIVETo study the effects of salidroside on the function and ultramicro-pathological change of the hypothalamic-pituitary-gonadal (HPG) axis of male rats in experimental navigation and intensive exercise.

METHODSSix-week SD rats were randomized into 3 groups: non-stress control (NC, n = 10), training control (TC, n = 12) and salidroside treatment (ST, n = 12) group. Blood samples were collected from the NC rats that did not receive any stimulus after a 7-day intragastric administration of saline. The TC rats underwent a 10-day running training with increasing load on the treadmill followed by a 7-day intragastric administration of saline. The ST rats were subjected to the same process of running training as the TC group and received intragastric administration of salidroside. Then blood samples were immediately obtained and the levels of testosterone (T), corticosterone (CORT), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) measured by radioimmunoassay. The testis histopathology was observed by HE staining, and the ultrastructural changes of the pituitaries and testes investigated by electron microscopy.

RESULTSThe serum T level was significantly lower in the TC than in the NC group, but showed no significant difference between the ST and NC groups. HE staining revealed no significant difference in testis histopathology among the 3 groups. Ultramicro-pathology showed that the secretory granules of the pituitary cells were significantly reduced in the TC rats compared with the NC ones; the number of the granules significantly increased in the ST group compared with the TC rats; and mitochondrial swelling, increase of electron density and decrease/disappearance of mitochondrial cristae were observed in the Leydig cells of the TC rats. But no significant differences were found in the testicular cells between the ST and NC groups.

CONCLUSIONNegative psychological stress and intensive exercise can significantly suppress the function of the HPG axis in rats. Salidroside therapy has protective effect on the HPG axis.

Animals ; Glucosides ; pharmacology ; therapeutic use ; Hypothalamo-Hypophyseal System ; drug effects ; pathology ; Male ; Phenols ; pharmacology ; therapeutic use ; Physical Conditioning, Animal ; Pituitary Gland ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley ; Rhodiola ; chemistry ; Stress, Psychological

OBJECTIVETo investigate the effects of schisandra on the function of the pituitary-adrenal cortex, gonadal axis and carbohydrate metabolism in male rats undergoing experimental chronic psychological stress, navigation and strenuous exercise.

METHODSThirty-four SD rats were randomly allocated into a non-stress group (Group A), a stress control group (Group B) and a schisandra group (Group C). The latter two groups received 10 days of Benford's high-intensity training, followed by 3 hours of wearing floating with psychological stress and another 3 hours of running at the speed of 26.7 m/min. Then blood samples were immediately obtained for the measurement of the levels of testosterone (T), corticosterone (CORT), luteinizing hormone (LH) and blood glucose (Glu). Meanwhile the adrenal gland was excised and its cortex ultrastructure observed under the electron microscope.

RESULTSThe Glu level was increased while the T level decreased significantly in Group B as compared with Group A. The CORT level remained unchanged in Group B. Both the Glu and CORT levels were significantly reduced in Group C in comparison with B. However, no significant differences were found in serum LH levels among the three groups. And electron microscopy revealed a reduction of lipid droplets and apoptosis of the adrenal cortex cells in Group B as compared with C.

CONCLUSIONSchisandra can reduce the levels of CORT and Glu and protect the structure of the adrenal cortex.

Animals ; Blood Glucose ; Carbohydrate Metabolism ; Corticosterone ; blood ; Cyclooctanes ; pharmacology ; Hyperkinesis ; Lignans ; pharmacology ; Male ; Physical Conditioning, Animal ; Phytotherapy ; Pituitary-Adrenal System ; metabolism ; Polycyclic Compounds ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Schisandra ; chemistry ; Stress, Psychological ; metabolism