مجله فیزیولوژی و فارماکولوژی ایران
سال چهارم شماره 1 (پیاپی 13، بهار و تابستان 1399)

Drug addiction is a chronic disease with biological, psychological and social consequences that includes three stages of drug use, withdrawal and relapse. The relapse is considered as the main obstacle to the treatment of addiction. In spite of extensive researches on neurobiological mechanisms of relapse using a variety of chemical and electrical methods, the rate of relapse to drug use is 40–60 percent within a year after the cessation of treatment and it has remained unchanged for the half a century ago. On the other hand, most studies in the field of addiction have been performed on laboratory animal models that results cannot be translated into clinical studies precisely, however, most available treatments are still relatively ineffective, because little information is available on the molecular and cellular underlying mechanisms of relapse. Therefore, given the importance of recognizing of relapse, in this review article we evaluate physiologically this phenomenon from various aspects, including the animal models, cellular-molecular mechanisms, predisposing factors, biomarkers, chemical, electrical, cognitive behavioral and Iranian traditional medicine treatment approaches, in the hope that researches on addiction treatment should be evaluated more purposefully than before.

Adolescence is considered as a critical developmental period during which long-lasting changes occur in the brain. Accumulating evidence support the growing non-medical use of morphine during adolescence. However, the long-term neurobiological and behavioral effects of opiate exposure during this stage are still remained largely unexplored. The present study examined the long term effects of adolescent morphine exposure on withdrawal signs and the negative motivational aspects of morphine withdrawal syndrome induced by naloxone in adult morphine dependent rats.

Adolescent male Wistar rats (30 days old) were administered increasing doses of morphine (from 2.5 to 25 mg/kg, s.c.) every 12 h, for 10days. Control rats received saline with the same protocol. Thereafter, during adulthood (65 days old), they were rendered dependent on morphine and tested for opioid withdrawal-induced conditioned place aversion to investigate the negative motivational aspects of withdrawal syndrome induced by naloxone.

Results showed that adolescent morphine treatment significantly increases the expression of morphine withdrawal signs and potentiates naloxone-induced conditioned place aversion in adult morphine dependent rats.

It can be concluded that chronic morphine treatment during adolescence in rats causes prolonged behavioral (and most probably neurobiological) changes in the central nervous system, which results in alteration of morphine withdrawal in adulthood.

Since products extracting from medicinal plants play an important role in the treatment of cancer, this study was performed to investigate the cytotoxicity effects of the total extracts obtained from the leaves of Dracocephalum moldavica (L.) treated with different elicitors on four human cancer cell lines.

Following cultivating the Dracocephalum moldavica in Kerman for two years, foliar spraying was carried out using salicylic acid and beta-aminobutyric acid at 0, 0.5 and 1 mM concentrations one month before harvesting. Then, the cytotoxic effect of each extract at two concentrations; 0.25 and 0.125 mg/ml was evaluated towards four human cancer cell lines at 5 replications using MTT assay. 3-5 × 103 number of the cells were seeded in 96-well plates and the percentage of cytotoxicity was determined after 72 h of incubation.

Among the four cancer cell lines, liver and breast cancer cells demonstrated the most sensitivity against the total extracts obtaining from the treated leaves of D.moldavica depending on the type treatment with different amounts of salicylic acid and beta-aminobutyric acid elicitors at two concentrations; 0.25 and 0.125 mg/ml after 72 hours of incubation. Results also showed that the lowest sensitivity to the extracts belonged to the colorectal carcinoma cells at two concentrations. Usage of both salicylic acid and beta-aminobutyric acid as elicitors in the process of plant growth increased the percentage of cytotoxicity on Hep-G2 cell line, while it had no remarkable effect on HT-29 cells.

Total extracts obtaining from the treated leaves of D. moldavica at a high concentration displayed a considerable cytotoxicity towards human breast and hepatocellular carcinomas. Indeed, further studies are needed to separate the constituents of the extracts and investigate their effects.

Research on the effects of resistance training on fibroblast growth factor 21 (FGF21) and βKlotho protein expression in patient with nonalcoholic fatty liver disease (NAFLD) is limited. We aimed to determine effects of eight weeks resistance training on serum level of βKlotho and FGF21 in diabetic women with NAFLD.

Thirty diabetic women (age 53 ± 7, height 158±4, weight 75 ± 9) with NAFLD participated in this study Subjects were randomly divided into two groups of control (n = 15) and exercise (n = 15). The training group performed resistance training of upper and lower body muscles in 3 sets of 50% - 70% of one repetition and 10-16 repeat in each session and three sessions per week for eight weeks. The control group did not perform any exercise program. Leg and chest muscle strength was measured by one repetition maximum (1RM) test. Serum level of βklotho and FGF21were measured by ELISA technique. Two-way ANOVA test with repeated measures with p < 0.05 was used to determine the significant differences.

Except for βKlotho and insulin serum levels, none of the other variables of the control group showed significant difference in pre and post training. However, in the training group, weight, fat percent, body mass index, Waist to hip ratio, insulin, glucose, βKlotho and FGF21 levels were significantly changed after training (p < 0.05). A significant difference was observed between control and training groups in βKlotho and FGF21 levels (p < 0.05).

Resistance training could improve imbalance of FGF21 and βKlotho protein expression in women with type 2 diabetes and NAFLD.

Research on the effects of endurance training on fibroblast growth factor 21 (FGF21) and βKlotho protein expression in patient with nonalcoholic fatty liver disease (NAFLD) is limited. We aimed to determine effects of eight weeks endurance training with moderate intensity on FGF21 and βKlotho protein expression in diabetic women with NAFLD.

Thirty diabetic women (age 53 ± 7, height 158 ± 4, weight 75 ± 9) with NAFLD participated in this study Subjects were randomly divided into two groups of control (n = 15) and exercise (n = 15). The training was performed by running in each session for 30-45 min with 60-70% of the heart rate reserve and three sessions per week for eight weeks. Control group did not perform any exercise program. Rockport walking test and ELISA technique were used to measure VO2max and βKlotho and FGF21 protein expression, respectively. Two-way ANOVA test with repeated measures and p < 0.05 was used to determine the significant differences.

Except for βKlotho serum level, none of the other variables of the control group showed significant difference in pre and post training. However, in the training group, weight, fat percent, body mass index, Waist to hip ratio, insulin, glucose, βKlotho and FGF21 levels were significantly changed after training (p < 0.05). A significant difference was observed between control and training groups in βKlotho and FGF21 levels (p < 0.05).

Endurance training could improve imbalance of FGF21 and βKlotho protein expression in women with type 2 diabetes and NAFLD.

Carpal Tunnel Syndrome (CTS) is the most common neuropathy of the median nerve. There is enough empirical evidence to show that statins may have neuroprotective effect other than cholesterol reduction. In this research we investigated the effect of rosuvastatin on the clinical symptoms in patients with mild to moderate CTS.

In this interventional study, 50 patients with mild to moderate CTS participated in both treatment and control groups. Rosuvastatin 20 mg and placebo were administered daily to the treatment and control group respectively. The Nerve conduction study was performed on the third finger of all patients by two neurologists. The Visual Analogue is an acceptable scale to measure the amount of pain that a patient feels. Based on the electrodiagnosis method the neuropathy of the median nerve evaluated by measurements of the sensory and motor nerve conduction delay. The severity of symptoms and performance status of patients were also assessed by the Boston questionnaire.

The pain index in the treatment group after intervention was 3.91 ± 2.69 that showed a significant decrease (p = 0.025) compare to before intervention (5.8 ± 3.2), but there was no significant difference in terms of symptom severity and functional status before and after the intervention.

Rosuvastatin can be effective especially in reducing the pain associated with CTS. We believe this positive effect can have a marked effect on the patients' quality of life and reduce the pain-associated problems.

The aim of the present study was to investigate the effect of aerobic training on consolidation of spatial memory and CREB protein index in the hippocampal tissue of sleep deprived young rats.

Forty Wistar young male rats were randomly assigned to four groups: sedentary/normal sleep control group (Cr), sedentary/sleep deprived (Sd), physical activity/normal sleep (Ph/Ns) and physical activity/ sleep deprived (Ph/Sd). Physical activity was included four weeks aerobic training by running on treadmill. Rats performed aerobic training 5 days/week for 4 weeks by running on a treadmill with a zero-degree slope. In the first and second weeks rats ran for 2 sets of 15 min with speed of 10 m/min. In the third week, 3 sets of 15 min with speed of 15 m/min was performed. In the fourth week, 4 sets of 15 min with speed of 15 m/min was done. After aerobic training, the memory acquisition was asesseded by Morris water maze. Then, sleep deprivation was induced in rats of Sd and Ph/Sd groups for 24 h by a multiple platform device. The spatial memory consolidation was tested 24 h after sleep deprivation. Western blot technique was used to measure the CERB protein index in the hippocampus.

Aerobic training improved acquisition and consolidation of spatial memory while sleep deprivation destroyed the spatial memory (p ˂ 0.05). However, aerobic training prevented the destruction of spatial memory consolidation induced by sleep deprivation. Aerobic training also increased expression of CERB but sleep deprivation had no significant effect on the expression of CERB. However, the effect of aerobic training on the expression of CERB in the sleep deprived rats was significant (p < 0.05).

It seems that aerobic training on treadmill is able to prevent the adverse effects of sleep deprivation on the spatial memory consolidation in rats.

Effect of high intensity interval training (HIT) and low intensity continuous training was examined on Phospholipid Transfer Protein (PLTP), Cholesteryl Ester Transfer Protein (CETP) and CCAAT-enhancer-binding proteins (CEBP/α) genes expression after 13 weeks high fat diet (HFD) in rats. Male Wistar rats were assigned in three groups including control, HIT and LIT after 13 weeks high fat diet (HFD). Trainings were performed for 12 weeks (5 days per week). PLTP and C/EBPα genes expression in HIT group was found higher than LIT and control groups (p ≤ 0.05) but no difference was observed between LIT and control groups (p > 0.05). CETP gene expression in HIT group was higher than LIT and control groups, and in LIT group was higher than control group (p ≤ 0.05). Thus, HIT trainings are more effective than LIT trainings in elevation of PLTP, CETP and CEBP/α genes expression in rats.