Inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) is a chronic and disabling disease with unknown etiology. There have been some controversies regarding the ...role of psychological factors in the course of IBD. The purpose of this paper is to review that role. First the evidence on role of stress is reviewed focusing on perceived stress and patients’ beliefs about it in triggering or exacerbating the course of IBD. The possible mechanisms by which stress could be translated into IBD symptoms, including changes in motor, sensory and secretory gastrointestinal function, increase intestinal permeability, and changes in the immune system are, then reviewed. The role of patients’ concerns about psychological distress and their adjustment to disease, poor coping strategies, and some personality traits that are commonly associated with these diseases are introduced. The prevalence rate, the timing of onset, and the impact of anxiety and depression on health-related quality of life are then reviewed. Finally issues about illness behavior and the necessity of integrating psychological interventions with conventional treatment protocols are explained.
There is evidence that lesions of the nucleus accumbens core (AcbC) promote preference for smaller earlier reinforcers over larger delayed reinforcers in inter-temporal choice paradigms. It is not ...known whether this reflects an effect of the lesion on the rate of delay discounting, on sensitivity to reinforcer magnitude, or both.
We examined the effect of AcbC lesions on inter-temporal choice using a quantitative method that allows effects on delay discounting to be distinguished from effects on sensitivity to reinforcer size.
Sixteen rats received bilateral quinolinic acid-induced lesions of the AcbC; 14 received sham lesions. They were trained under a discrete-trials progressive delay schedule to press two levers (A and B) for a sucrose solution. Responses on A delivered 50 microl of the solution after a delay d(A); responses on B delivered 100 microl after d(B). d(B) increased across blocks of trials, while d(A) was manipulated across phases of the experiment. Indifference delay d(B(50)) (value of d(B) corresponding to 50% choice of B) was estimated in each phase, and linear indifference functions (d(B(50)) vs d(A)) derived.
d(B(50)) increased linearly with d(A) (r(2) > 0.95 in each group). The intercept of the indifference function was lower in the lesioned than the sham-lesioned group; slope did not differ between groups. The lesioned rats had extensive neuronal loss in the AcbC.
The results confirm that lesions of the AcbC promote preference for smaller, earlier reinforcers and suggest that this reflects an effect of the lesion on the rate of delay discounting.
The dopamine-releasing agent d-amphetamine and the 5-HT(2) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) have similar effects on free-operant timing behavior. The selective D(1) dopamine ...receptor antagonist 8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SKF-83566), but not the D(2) dopamine receptor antagonist haloperidol, can antagonize the effect of d-amphetamine, and the selective 5-HT(2A) receptor antagonist (+/-)2,3-dimethoxyphenyl-1-(2-(4-piperidine)-methanol (MDL-100907) can antagonize the effect of DOI. However, it is not known whether the effect of d-amphetamine can be reversed by MDL-100907 and the effect of DOI by dopamine receptor antagonists.
The objective of this work is to examine the interactions of d-amphetamine and DOI with MDL-100907, SKF-83566, and haloperidol on timing performance.
Rats (n = 12-15 per experiment) were trained under the free-operant psychophysical procedure to press two levers (A and B) in 50-s trials in which reinforcement was provided intermittently for responding on A in the first half, and B in the second half of the trial. Percent responding on B (%B) was recorded in successive 5-s epochs of the trials; logistic functions were fitted to the data from each rat for the derivation of timing indices T (50) (time corresponding to %B = 50); Weber fraction. Rats were treated systemically with d-amphetamine or DOI, alone and in combination with haloperidol, SKF-83566, or MDL-100907.
d-Amphetamine (0.4 mg kg(-1)) reduced T (50) compared to vehicle; this effect was antagonized by SKF-83566 (0.03 mg kg(-1)) and MDL-100907 (0.5 mg kg(-1)), but not by haloperidol (0.05, 0.1 mg kg(-1)). DOI (0.25 mg kg(-1)) also reduced T (50); this effect was reversed by MDL-100907 (0.5 mg kg(-1)), but not by SKF-83566 (0.03 mg kg(-1)) or haloperidol (0.05 mg kg(-1)).
The results suggest that both 5-HT(2A) and D(1) receptors, but not D(2) receptors, are involved in d-amphetamine's effect on timing behavior in the free-operant psychophysical procedure. DOI's effect on timing is mediated by 5-HT(2A) receptors, but neither D(1) nor D(2) receptors are involved in this effect.
Mesenchymal stem cells (MSCs) have the ability to migrate into tumor sites and release growth factors to modulate the tumor microenvironment. MSC therapy have shown a dual role in cancers, promoting ...or inhibiting. However, MSCs could be used as a carrier of anticancer agents for targeted tumor therapy. Recent technical improvements also allow engineering MSCs to improve tumor-targeting properties, protect anticancer agents, and decrease the cytotoxicity of drugs. While some of MSC functions are mediated through their secretome, MSCs-derived extracellular vesicles (EVs) are also proposed as a possible viechle for cancer therapy. EVs allow efficient loading of anticancer agents and have an intrinsic ability to target tumor cells, making them suitable for targeted therapy of tumors. In addition, the specificity and selectivity of EVs to the tumor sites could be enhanced by surface modification. In this review, we addressed the current approaches used for engineering MSCs and EVs to effectively target tumor sites and deliver anticancer agents.
Graphical abstract. Engineering MSCs and their EVs to target and destroy tumors. MSC: mesenchymal stem cell, EVs: Extracellular vesicles, miRNA: microRNA. Display omitted
Temporal differentiation of operant behaviour is sensitive to dopaminergic manipulations. Studies using the fixed-interval peak procedure implicated D2 dopamine receptors in these effects. Less is ...known about the effects of dopaminergic manipulations on temporal differentiation in other timing schedules.
To examine the effects of a D1 antagonist,8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SKF-83566), and a D2 antagonist, haloperidol, on performance on the free-operant psychophysical procedure, and the ability of these antagonists to reverse the effects of the catecholamine-releasing agent, d-amphetamine on performance. The antagonists' ability to reverse d-amphetamine-induced hyperlocomotion was also examined.
Rats responded on two levers (A and B) under a free-operant psychophysical schedule, in which reinforcement was provided intermittently for responding on A during the first half, and B during the second half, of 50-s trials. Logistic functions were fitted to the relative response rate data (percent responding on B %B vs time t) in each treatment condition, and quantitative timing indices T50 (value of t corresponding to %B=50) and Weber fraction were compared among treatments. Effects of the treatments on locomotion were measured in a separate experiment.
SKF-83566 (0.015, 0.03, 0.06 mg kg(-1)) did not affect timing performance. Haloperidol (0.025, 0.05 mg kg(-1)) had no effect; a higher dose (0.1 mg kg(-1)) reduced T (50). d-Amphetamine (0.4 mg kg(-1)) reduced T50; this effect was antagonised by SKF-83566 but not by haloperidol. Both antagonists reduced d-amphetamine-induced hyperlocomotion.
The results suggest that d-amphetamine's effect on performance in the free-operant psychophysical procedure is mediated by D1 rather than D2 receptors.
Performance on progressive ratio schedules has been proposed as a means of assessing the effects of drugs on the value or "efficacy" of reinforcers. A mathematical model affords a basis for ...quantifying the effects of drugs on progressive ratio schedule performance. According to this model, the relation between response rate and ratio size is described by a bitonic (inverted-U) function. One parameter of the function, alpha, expresses the motivational or "activating" effect of the reinforcer (duration of activation of responding produced by the reinforcer), whereas another parameter, delta, expresses the minimum time needed to execute a response, and is regarded as an index of "motor capacity". In a previous experiment we found that the "atypical" antipsychotic clozapine increased alpha, indicating an increase in the efficacy of a food reinforcer.
We examined the effects of four "atypical" and four "conventional" antipsychotics on progressive ratio schedule performance.
Rats responded for a sucrose reinforcer (0.6 M, 50 microl) on a time-constrained progressive ratio schedule (50-min sessions). After 90 preliminary training sessions, they received acute doses of antipsychotics (doses in mg kg(-1)): atypical: clozapine (2, 4, 8, IP; n=15), quetiapine (1.25, 2.5, 5, 10, SC; n=23), olanzapine (0.25, 0.5, 1, IP; n=15), ziprasidone (0.625, 1.25, 2.5, IP, n=15); conventional: haloperidol (0.025, 0.05, 0.1, IP, n=15), pimozide (0.125, 0.25, 0.5, IP; n=15), raclopride (0.25, 0.5, 1, SC; n=12), cis-flupenthixol (0.2, 0.4, 0.8, SC; n=15). Values of a and delta were estimated from the response rate functions obtained under each treatment condition, and were compared between drug and vehicle-alone treatments.
The atypical antipsychotics significantly increased alpha (indicating enhancement of reinforcer efficacy), and also increased delta (indicating reduction of motor capacity). Haloperidol, pimozide and raclopride significantly increased delta; none of the conventional antipsychotics significantly altered alpha.
The results extend previous findings with clozapine to other atypical antipsychotics and suggest that enhancement of the efficacy of reinforcers may be a common feature of atypical antipsychotics not shared by conventional antipsychotics.
Background & aim: One of the most critical stages of women's lives is menopause. It is caused by permanent cessation of ovarian function and decreased of estrogen level. Menopause has numerous side ...effects (Physical and psychological). Recent neurophysiological data suggest that the function of central nervous system may be susceptible to modulation by estrogen. The aim of this study was to compare the performance of the five important parts (prefrontal cortex, cingulate gyrus, limbic system, basal ganglia and temporal cortex) of the brain and mood changes (anxiety and depression) with the level of estrogen in postmenopausal and premenopausal women in Isfahan. Methods: In the present descriptive study 200 women (100 postmenopausal women 45 to 65 years old and 100 women, premenopausal 20 to 40 years old) were selected by sequentially available from health centers of Motahari, Sajjad and Amin Askariyeh Hospital. The research instrument was a brain systems questionnaire of 101 questions (Brain systems) with 89/0 reliability to evaluate five important system functions in the brain (prefrontal cortex, cingulate gyrus, limbic system, basal ganglia and temporal lobe) and Beck Depression Inventory with reliability of 93 / 0 and anxiety with reliability 92/0 to assess depression and anxiety. The data was analyzed using descriptive statistics (mean and standard deviation) and inferential statistics (MANOVA MANOVA) analysis. Results: significant differences were found in five brain system functions (prefrontal cortex, cingulate gyrus, limbic system, basal ganglia and temporal cortex) and levels of estrogen and anxiety of two the groups of postmenopausal and premenopausal women (P<0.001) but no significant difference was observed regarding depression of these groups (P>0/001). Conclusion: It seems that in addition to the role of estrogen in the female reproductive system, it also has an impact on the nervous system and its various parts. Following the reduction of estrogen in postmenopausal women, the modulation of brain functions is affected. So the two-way interaction and convergence among secretion of hormones with brain function and mood changes such as anxiety and depression could be explained.
Performance on progressive ratio schedules has been proposed as a means of assessing the effects of drugs on the efficacy of reinforcers. A mathematical model (Killeen PR (1994) Mathematical ...principles of reinforcement. Behav Brain Sci 17:105-172) affords a basis for quantifying the effects of drugs on progressive ratio schedule performance. The model postulates a bitonic function relating response rate and ratio size. One parameter of the function, a, expresses the motivational effect of the reinforcer, whereas another parameter, delta, expresses the minimum time needed to execute a response, and is regarded as an index of 'motor capacity'. Previously we found that the atypical antipsychotic clozapine increased a, indicating an increase in reinforcer efficacy; a similar effect was observed with the 5-hydroxytryptamine (5-HT)(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). It has been suggested that some of clozapine's behavioural effects are mediated by agonistic action at 5-HT(1A) receptors.
This study was conducted to compare the effects of clozapine and 8-OH-DPAT on progressive ratio schedule performance.
Rats were trained under a time-constrained progressive ratio schedule (50-min sessions). In experiment 1, they received acute doses of clozapine (4 mg kg(-1)) and 8-OH-DPAT (100 microg kg(-1)), alone and in combination with the 5-HT(1A) receptor antagonist N-2-(4-2-methoxyphenyl-1-piperazinyl)ethyl-N-2-yridinylcyclohexanecarboxamide (WAY-100635; 30 microg kg(-1)). In experiment 2, the effects of clozapine (2, 4 and 8 mg kg(-1)) and 8-OH-DPAT (25, 50 and 100 microg kg(-1)) were compared between intact rats and rats whose 5-HTergic pathways had been ablated by 5,7-dihydroxytryptamine (5,7-DHT).
In both experiments, clozapine and 8-OH-DPAT increased a and delta. In experiment 1, WAY-100635 abolished the effect of 8-OH-DPAT on a and delta, but did not alter clozapine's effects on these parameters. In experiment 2, the effects of clozapine and 8-OH-DPAT did not differ between sham-lesioned and 5,7-DHT-lesioned rats.
The results confirm previous findings on the effects of clozapine and 8-OH-DPAT on progressive ratio schedule performance. 8-OH-DPAT's effects are probably mediated by post-synaptic 5-HT(1A) receptors; clozapine's effects are mediated by a different mechanism, which does not appear to involve 5-HT(1A) receptors and which does not depend upon an intact 5-HTergic pathway.
We examined the effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-HT(2A/2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) on performance on the ...fixed-interval peak procedure, and the sensitivity of these effects to 5-HT1A and 5-HT2A receptor antagonists (N-2-(4-2-methoxyphenyl-1-piperazinylethyl-N-2-pyridinylcyclohexanecarboxamide WAY-100635 and ketanserin). Rats were trained to press a lever for food reinforcement in 50 min sessions consisting of 32 trials in which the lever was continuously available, separated by 10 s inter-trial intervals. In 16 trials, reinforcement was delivered following the first response after 30 s had elapsed since trial onset (fixed-interval 30 s). In 16 randomly interposed (peak/probe) trials, reinforcement was omitted, and the lever remained in the operant chamber for 120 s. Response rate in probe trials was plotted against time from trial onset. Time to peak response rate (t(peak)) and the Weber fraction were derived from modified Gaussian curves fitted to each rat's data. 8-OH-DPAT (0.05 mg kg(-1)) reduced t(peak) and increased the Weber fraction; the effect on t(peak) was antagonized by WAY-100635 (0.1 mg kg(-1)). DOI (0.25 mg kg(-1)) also reduced t(peak) and increased the Weber fraction; the reduction of t(peak) was antagonized by ketanserin (2 mg kg(-1)). Stimulation of 5-HT1A and 5-HT2A receptors alters temporal differentiation in qualitatively similar ways.
Temporal differentiation refers to animals' ability to regulate their behaviour during an ongoing interval. Striatal dopaminergic mechanisms are purported to be involved in temporal differentiation, ...and recent evidence also implicates 5-hydroxytryptaminergic (5-HTergic) mechanisms, possibly mediated by 5-HT(2A) receptors. There is evidence that 5-HT(3) receptors contribute to the regulation of dopamine release in the basal ganglia; however, it is not known whether 5-HT(3) receptor stimulation can influence temporal differentiation.
We examined the effects of a selective 5-HT(3) receptor agonist m-CPBG, a mixed 5-HT(2A/3) receptor agonist quipazine, and selective 5-HT(3) and 5-HT(2A) receptor antagonists (MDL-72222 and ketanserin, respectively) on temporal differentiation in a free-operant psychophysical procedure.
Twenty-four rats were trained to respond on two levers (A and B) under a free-operant psychophysical schedule, in which sucrose reinforcement (0.6 M: , 50 microl) was provided intermittently for responding on A during the first half and on B during the second half of 50-s trials. Logistic psychometric functions were fitted to the relative response rate data percent responding on B (%B) vs time from trial onset (t), and quantitative indices of timing performance T (50) (value of t corresponding to %B=50), Weber fraction, and mean time of switching from A to B, S (50) were derived.
Quipazine (0.5, 1, and 2 mg kg(-1)) altered timing performance, dose-dependently reducing T (50) and S (50); m-CPBG (2.5, 5, and 10 mg kg(-1)) had no significant effect. The effect of quipazine was antagonized by ketanserin (2 mg kg(-1)), but not by MDL-72222 (1 mg kg(-1)).
The present results provide no evidence for the involvement of 5-HT(3) receptors in temporal differentiation and indicate that the effect of quipazine on performance was mediated by 5-HT(2A) receptor stimulation. The results are consistent with previous evidence for the involvement of 5-HT(2A) receptors in interval timing behaviour.
PDF
