Anticipating influential factors on suicide outcomes through machine learning techniques: Insights from a suicide registration program in western Iran.

Suicide is a global public health concern, with increasing rates observed in various regions, including Iran. This study focuses on the province of Hamadan, Iran, where suicide rates have been on the rise. The research aims to predict factors influencing suicide outcomes by leveraging machine learning techniques on the Hamadan Suicide Registry Program data collected from 2016 to 2017. The study employs Naïve Bayes and Random Forest algorithms, comparing their performance to logistic regression. Results highlight the superiority of the Random Forest model. Based on the variable importance and multiple logistic regression analyses, the most important determinants of suicide outcomes were identified as suicide method, age, and timing of attempts, income, and motivation. The findings emphasize the cultural context's impact on suicide methods and underscore the importance of tailoring prevention programs to address specific risk factors, especially for older individuals. This study contributes valuable insights for suicide prevention efforts in the region, advocating for context-specific interventions and further research to refine predictive models and develop targeted prevention strategies.

Trans-generational effects of parental exposure to drugs of abuse on offspring memory functions.

Recent evidence reported that parental-derived phenotypes can be passed on to the next generations. Within the inheritance of epigenetic characteristics allowing the transmission of information related to the ancestral environment to the offspring, the specific case of the trans-generational effects of parental drug addiction has been extensively studied. Drug addiction is a chronic disorder resulting from complex interactions among environmental, genetic, and drug-related factors. Repeated exposures to drugs induce epigenetic changes in the reward circuitry that in turn mediate enduring changes in brain function. Addictive drugs can exert their effects trans-generally and influence the offspring of addicted parents. Although there is growing evidence that shows a wide range of behavioral, physiological, and molecular phenotypes in inter-, multi-, and trans-generational studies, transmitted phenotypes often vary widely even within similar protocols. Given the breadth of literature findings, in the present review, we restricted our investigation to learning and memory performances, as examples of the offspring's complex behavioral outcomes following parental exposure to drugs of abuse, including morphine, cocaine, cannabinoids, nicotine, heroin, and alcohol.

Balance-energy of resting state network in obsessive-compulsive disorder.

Stability of the brain functional network is directly linked to organization of synchronous and anti-synchronous activities. Nevertheless, impact of arrangement of positive and negative links called links topology requires to be well understood. In this study, we investigated how topology of the functional links reduce balance-energy of the brain network in obsessive-compulsive disorder (OCD) and push the network to a more stable state as compared to healthy controls. Therefore, functional associations between the regions were measured using the phase synchrony between the EEG activities. Subsequently, balance-energy of the brain functional network was estimated based on the quality of triadic interactions. Occurrence rates of four different types of triadic interactions including weak and strong balanced, and unbalanced interactions were compared. In addition, impact of the links topology was also investigated by looking at the tendency of positive and negative links to making hubs. Our results showed although the number of positive and negative links were not statistically different between OCD and healthy controls, but positive links in OCDs' brain networks have more tendency to make hub. Moreover, lower number of unbalanced triads and higher number of strongly balanced triad reduced the balance-energy in OCDs' brain networks that conceptually has less requirement to change. We hope these findings could shed a light on better understanding of brain functional network in OCD.

Gender and age differences in suicide attempt: A large population study in the West of Iran.

Present study was to evaluate the relationship between suicide attempt, gender and age. We used all of suicide attempt entered in Hamadan Suicide Registry Program (2016-2017). Finding revealed that suicide attempt was lower among elderly patients. Using poison and self-immolation was more common in elder patients. Suicide attempt in females against males was higher in married. In males the higher rate of suicide attempt was in autumn, while in females was in summer. Using of drug was more frequent in females, while self-harm was more common in males. Gender and age are important risk factors of suicide attempts.

Effect of acute and chronic restraint stress on electrical activity of prefrontal cortex neurons in the reinstatement of extinguished methamphetamine-induced conditioned place preference: An electrophysiological study.

Increased vulnerability to drug abuse has been observed after exposure to stress and the prefrontal cortex (PFC) plays a major role in the control of the stress response and reward pathway. The current study was conducted to clarify the effects of acute and chronic restraint stress on PFC neural activity during the reinstatement of methamphetamine (METH)-induced conditioned place preference (CPP) in rats. Following the establishment of CPP (METH 0.5 mg/kg; s.c. for 3 days) and the extinction phase, male Wistar rats were divided into threshold (0.25 mg/kg; s.c.) and sub-threshold (0.125 mg/kg; s.c.) METH-treated super groups to induce reinstatement. Each super group contained control (non-stressed), acute restraint stress (ARS) and chronic restraint stress (CRS) groups. in vivo single unit recordings were performed on the urethane-anesthetized rats in these groups. After baseline recordings (10-min period) of the neurons in the PFC, their firing activity was recorded for 50 min during the reinstatement phase after injection of METH. The results showed that the threshold dose, but not the sub-threshold dose, of METH significantly increased PFC neural activity in the non-stressed animals. The sub-threshold dose of METH notably changed this activity in both the ARS and CRS groups. These changes in the excited neurons after the sub-threshold dose in the ARS and CRS groups were significantly higher than those in the non-stressed group. It appears that the PFC is implicated in the associated reward pathway and stress functions. METH affected the firing rate of PFC neurons and stress amplified the effect of METH on changes in the neuronal firing rate in the PFC.

Involvement of orexinergic receptors in the nucleus accumbens, in the effect of forced swim stress on the reinstatement of morphine seeking behaviors.

Orexinergic system is involved in primary rewards; the neural circuit of the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex and amygdala represents overlapping elements mediating the rewarding effects of drugs and stressful experiences. The NAc integrates reward-related information from the VTA. Also, it has been indicated that orexinergic system activates the mesolimbic dopamine projecting neurons to the NAc and promotes the development of reward in rodents. Therefore, in the present study, the conditioned place preference (CPP) paradigm was used to determine the role of the two types of orexin receptors (OXR) in the NAc in forced swim stress (FSS), as physical stress, and/or priming-induced reinstatement of morphine. The CPP was induced by injecting morphine (5 mg/kg, SC for 3 days) and lasted for eight free-morphine days; the reinstatement was induced by administration of effective priming dose of morphine (1 mg/kg; sc). The extinguished rats received intra-NAc injection of SB334867 as OX1R antagonist or TCSOX229 as OX2R antagonist before effective priming dose injection of morphine (1 mg/kg; sc). In others, the extinguished rats were given intra-NAc injection of SB334867 or TCSOX229 and then, they underwent FSS before injection of ineffective priming dose of morphine (0.5 mg/kg; sc). Our results showed that intra-accumbal administration of SB334867 or TCSOX229 could inhibit morphine priming- and FSS-induced reinstatement of extinguished morphine-seeking in the rats. It seems that OXR in the NAc may be involved in reward and could play an important role in the effect of stress on reinstatement of morphine-seeking behaviors in this area.

Effects of Acute and Chronic Restraint Stress on Reinstatement of Extinguished Methamphetamine-induced Conditioned Place Preference in Rats.

INTRODUCTION: Methamphetamine (METH) is a neurotoxic psychostimulant with highly addictive potential that leads to compulsive drug use and vulnerability to relapse. Environmental cues, such as drug exposure, peer influence, and social stress, are the powerful triggers of drug relapse. In this study, we tried to find out the effect of acute and chronic restraint stress on reinstatement of extinguished METH-induced Conditioned Place Preference (CPP) in rats. METHODS: Subcutaneous (SC) administration of METH (0.125, 0.25, 0.5, 1, 2 and 4 mg/kg) could induce CPP and it was found that METH with the dose of 0.5 mg/kg was more potent than other doses. In extinction phase, rats were put in the CPP box for 30 min per day for 8 consecutive days. After extinction, animals were exposed to restraint stress (3-h period, as an acute stress) 60 min before subcutaneous administration of ineffective dose of METH (0.125 mg/kg) in order to reinstate the extinguished METH-induced CPP. For induction of the chronic stress during extinction phase, the animals were exposed to the restraint stress for one hour per day. RESULTS: The results showed that the effective dose of METH to induce CPP was 0.5 mg/kg. Based on the results, physical stress (restraint stress) whether acute and chronic, can significantly induce reinstatement of METH-induced CPP (P˂0.001) in extinguished animals. CONCLUSION: Additionally, the chronic restraint stress could reduce duration of extinction (maintenance) of METH-induced CPP. It seems that exposure to the stress induces the relapse in abstinent amphetamine, but acute and chronic situation have a different reaction.

Glucocorticoid receptors in the basolateral amygdala mediated the restraint stress-induced reinstatement of methamphetamine-seeking behaviors in rats.

Methamphetamine (METH) addiction is a growing epidemic worldwide. It is a common psychiatric disease and stress has an important role in the drug seeking and relapse behaviors. The involvement of the basolateral amygdala (BLA) in effects of stress on the reward pathway has been discussed in several studies. In this study, we tried to find out the involvement of glucocorticoid receptors (GRs) in the BLA in stress-induced reinstatement of the extinguished METH-induced conditioned place preference (CPP) in rats. The CPP paradigm was done in eighty-one adult male Wistar rats weighing 220-250 g. The animals received a daily injection of methamphetamine (0.5 mg/kg), during the conditioning phase. In extinction phase, the rats were put in the CPP box for 30 min per day for 8 days. After the extinction, the animals were exposed to acute restraint stress (ARS), 3 h before subcutaneous administration of sub-threshold dose of methamphetamine (0.125 mg/kg), based on our previous study, in reinstatement phase. In separated groups, the rats were exposed to chronic restraint stress (CRS) for 1 h each day during the extinction phase. To block the GRs in BLA, the animals unilaterally received RU38486 as GRs antagonist (10, 30 and 90 ng/0.3 µl DMSO) in all ARS groups on reinstatement day. In separated experiments, RU38486 (3, 10 and 30 ng/0.3 µl DMSO) was microinjected into the BLA in CRS groups prior to exposure to stress every day in extinction phase. The results revealed that intra-BLA RU38486 in ARS (90 ng) and CRS (10 and 30 ng) groups significantly prevented the stress-induced reinstatement. It can be proposed that stress partially exerts its effect on the reward pathway via GRs in the BLA. This effect was not quite similar in acute and chronic stress conditions.

Functional roles of orexin/hypocretin receptors in reward circuit.

Since its first discovery in 1998, it has become clear that the orexinergic system plays an important role in regulating a number of functions including food, sex, social connections, and most prominently reward-related behaviors. Orexinergic neurons in the lateral hypothalamus project extensively to other brain areas, two most important of which are the ventral tegmental area and the nucleus accumbens that are involved in reward processing. In this review, we have presented the work in our laboratory along with the work of others and have discussed the possible functions we can infer from the research. We discuss the anatomy of the orexinergic system and its components followed by a presentation of other connected brain areas. The second part of this review discusses observed results from the morphine conditioned place preference test that sheds light on the possible role of the involved areas in reward processing. The complex circuits involved in reward processing are only beginning to be understood and we need to deepen our understanding regarding the nature of the interactions between all brain areas involved.

Protective Effects of Cyperus Rotundus Extract on Amyloid ß-Peptide (1-40)-Induced Memory Impairment in Male Rats: A Behavioral Study.

INTRODUCTION: The Alzheimer Disease (AD) is the most common form of dementia that leads to memory impairment. As the oxidative stress plays an important role in AD pathogenesis, the current study aimed at examining the protective effects of Cyperus Rotundus as an antioxidant on amyloid ß (Aß)-induced memory impairment. METHODS: Twenty-eight Wistar male rats received intrahippocampal (IHP) injection of the Aß (1-40) and C. rotundus (400 mg/kg, intraperitoneally). Spatial memory was assessed by the Morris water-maze (MWM) task. RESULTS: In the MWM, Aß (1-40) significantly increased escape latency and traveled distance (P<0.001). The administration of C. rotundus attenuated the Aß-induced memory impairment in the MWM task. CONCLUSION: The current study findings showed that C. Rotundus could improve the learning impairment, following the Aß treatment, and it may lead to an improvement of AD-induced cognitive dysfunction.

The effects of methamphetamine and buprenorphine, and their interaction on anxiety-like behavior and locomotion in male rats.

Methamphetamine (Meth) abuse and dependence are major global problems. Most of previous studies showed that Meth is anxiogenic. While buprenorphine (Bup) is used to treat anxiety-related behaviors, the effects of Meth in combination with Bup on anxiety-like behavior are unclear. In this study, we examined the effects of these drugs on anxiety-like behavior with the elevated plus maze (EPM) and open field (OF) tests, which are widely used to assess anxiety-like behavior in small rodents. Forty male Wistar rats were divided into four groups: sham, Meth, Bup, and Bup+Meth. The groups were administered their assigned treatments for 7days. The time spent in the open arms, and number of total entries into the arms (total activity) in the EPM were recorded. In addition, locomotor activity and number of entrances into the center area in the OF were recorded. The 7-day administration of Meth or Bup increased open arm exploration in the EPM. In contrast, the combined administration of Bup and Meth had the opposite effects. In addition, Meth and Bup had no effects on total and locomotor activity. Furthermore, the rats in the Meth and Bup groups spent more time in the center of the OF, while the group given both Bup and Meth spent less time in the center of the OF. The administration of Meth and Bup alone was anxiolytic in rats, whereas the coadministration of Bup and Meth was anxiogenic.

Differential roles of orexin receptors within the dentate gyrus in stress- and drug priming-induced reinstatement of conditioned place preference in rats.

Orexins are hypothalamic peptides involved in the modulation of the feeding, arousal, reward function, learning, and memory; nevertheless, the role of orexins in stress and relapse are largely unclear. Therefore, in the present study, the reinstatement model were used to examine the effects of intradentate gyrus (DG) administration of SB334867 as an orexin-1 receptor antagonist and TCS OX2 29, as an orexin-2 receptor antagonist on drug priming- and forced swim stress (FSS)-induced reinstatement of morphine. One-hundred and 44 adult male albino Wistar rats weighing 200 g-280 g were bilaterally implanted by cannulas into the DG. For induction of conditioned place preference (CPP), subcutaneous (sc) injection of morphine (5 mg/kg) was used daily during a 3-day conditioning phase. Then, the conditioning score (conditional stimulus [CS]) was calculated. After a 24 hr "off" period following achievement of extinction criterion, rats were tested for drug priming-induced reinstatement by priming dose of morphine (1 mg/kg, sc) and for FSS-induced reinstatement 10 min after FSS. In the next experiments, animals received different doses of intra-DG administration of SB334867 and TCS OX2 29 (3, 10, and 30 µg/0.5 µl 12% DMSO per side), bilaterally and were subsequently tested for morphine priming- and FSS-induced reinstatement. Our findings indicated that the FSS-induced the reinstatement of seeking behaviors. Furthermore, intra-DG administration of orexin-1 and orexin-2 receptor antagonists attenuated drug priming-induced reinstatement dose-dependently. However, they have trivial role in FSS-induced reinstatement. It is concluded that drug priming-induced reinstatement may be mediated, at least in part, by stimulation of orexin receptors in the DG.

Involvement of dopaminergic receptors of the rat nucleus accumbens in decreasing the conditioned place preference induced by lateral hypothalamus stimulation.

Our previous study showed that chemical stimulation of the lateral hypothalamus (LH) by carbachol can produce conditioned place preference (CPP) in rats. Also, it has been indicated that orexin activates the mesolimbic dopamine projecting neurons to the nucleus accumbens (NAc) and promotes the development of reward in rodents. Therefore, in this study, we tried to determine the role of intra-accumbal D1 and D2 dopamine receptors in the development (acquisition) of reward-related behaviors induced by chemical stimulation of the LH. Eighty-eight adult male Wistar rats were unilaterally implanted by two separate cannulae into the LH and NAc. For chemical stimulation of LH, carbachol (250nmol/0.5µl saline) was microinjected once daily during 3-days conditioning phase (acquisition period) of CPP paradigm. In the next experiments, different doses of D1 receptor antagonist, SCH23390 (0.25, 1 and 4µg/0.5µl saline) or sulpiride (0.25, 1 and 4µg/0.5µl DMSO) as a D2 receptor antagonist were unilaterally microinjected into the NAc, 5min prior to LH stimulation. One-way ANOVA showed that intra-accumbal administration of SCH23390 or sulpiride can decrease the development of LH stimulation-induced CPP in the rats. However, this decrease is more effective after blockade of the D2 dopamine receptor in the NAc. It seems that the dopaminergic system in this area is involved in place preference induced by LH stimulation.

Intrahippocampal administration of D2 but not D1 dopamine receptor antagonist suppresses the expression of conditioned place preference induced by morphine in the ventral tegmental area.

The ventral tegmental area (VTA) as a major source of dopamine neurons projecting to cortical and limbic regions has a crucial role in reward and addiction. The current study assessed the role of D1 and D2 receptors within the dorsal hippocampus (CA1) in the expression of conditioned place preference (CPP) by intra-VTA morphine in the rats. In the present study, 160 adult male albino Wistar rats weighing 220-290g were bilaterally implanted by two cannulae into the CA1 and VTA. The CPP paradigm was done and animal displacement, conditioning score and locomotor activity were recorded. For blocking the dopamine D1/D2 receptors in the dorsal hippocampus, SCH23390 (0.02, 0.05, 0.2 and 0.5µg per side) or sulpiride (0.25, 0.75, 1.5 and 3µg per side) were microinjected into the CA1, just 5min before the CPP test on the post-conditioning day. All animals received intra-VTA morphine (1µg per side) during 3-days conditioning phase. Our results showed that sulpiride (1.5 and 3µg) but not SCH23390 in the dorsal hippocampus significantly decreased the expression of CPP induced by intra-VTA morphine (p<0.001). Intra-CA1 administration of these antagonists alone, in all doses, could not induce CPP. We suggest that D2 receptors in the CA1 region of hippocampus have a key role in the expression of CPP induced by morphine at the level of the VTA and there is a relationship between dopaminergic D2 receptors and opioidergic systems in these areas in reward circuit.

The Role of Resilience and Age on Quality of life in Patients with Pain Disorders.

The quality of life (QOL) has been defined as ''a person's sense of well-being that stems from satisfaction or dissatisfaction with the areas of life that are important to him/her''. Age was also significantly associated with several functional limitations such as illness, and physical restrictions. The concept of ''resilience'' refers to successful adaptation that unfolds within a context of significant and usually debilitating adversity or life stress. The ability to adapt to pain may play an important role in maintaining the QOL. In this study, we investigated the role of resilience and age in various domains of quality of life such as physical, psychological, social and environmental domains. In this study, 290 adult patients (146 men, 144 women) completed the Connor-Davidson Resilience Scale and the WHOQOL-BREF questionnaire. Moreover, we illustrated several demographic variables. The results were analyzed using SPSS version 19.0 and means, descriptive correlation and regression were calculated. Our data revealed that resilience and age could significantly anticipate the QOL and physical aspect (P<0.001). In psychological, social and environmental domains resilience but not the age could significantly predict this domains. In addition, it is noticeable that the effect of resilience on the prediction of QOL is much more obvious in the psychological domain.. In conclusion, resilience is more important factor than the age in prediction of life quality (QOL) in persons suffering from chronic pain.

Prediction of Quality of life by Self-Efficacy, Pain Intensity and Pain Duration in Patient with Pain Disorders.

The quality of life (QOL) has been defined as "a person's sense of well-being that stems from satisfaction or dissatisfaction with the areas of life that are important to him/her". It is generally accepted that pain intensity and duration have a negative impact on the QOL. One specific type of control is "self-efficacy", or the belief that one has the ability to successfully engage in specific actions. The ability to adapt to pain may play an important role in maintaining the QOL. In this study, we investigated the role of self-efficacy, pain intensity, and pain duration in various domains of quality of life such as physical, psychological, social and environmental domains. In this study, 290 adult patients (146 men, 144 women) completed coping self-efficacy and the WHOQOL-BREF Questionnaire. Moreover, we illustrated numerical rating scale for pain intensity. The results were analyzed using SPSS version of 19.0 and means, descriptive correlation, and regression were calculated. Our data revealed that self-efficacy but not the pain duration could significantly anticipate the QOL and its four related domains (P<0.001). In addition, it is noticeable that the effect of self-efficacy on the prediction of QOL is much more obvious in the psychological domain. However, the pain intensity could predict all of the QOL domains (P<0.001) except social and environmental ones. In conclusion, to predict the quality of life (QOL) in person suffering from chronic pain, self-efficacy and pain intensity are more important factors than the pain duration and demographic variables.

Orexin A in the ventral tegmental area induces conditioned place preference in a dose-dependent manner: involvement of D1/D2 receptors in the nucleus accumbens.

It has been shown that orexin A in the ventral tegmental area (VTA) is necessary for development of morphine place preference. Additionally, D1 and D2 dopamine receptors in the nucleus accumbens (NAc) have critical roles in motivation and reward. However, little is known about the function of orexin in conditioned place preference (CPP) in rats and involvement of D1/D2 receptors in the NAc. In the present study, we investigated the effect of direct administration of orexin A into the VTA, and examined the role of intra-accumbal dopamine receptors in development (acquisition) of reward-related behaviors in the rats. Adult male Wistar rats were unilaterally implanted by two separate cannulae into the VTA and NAc. The CPP paradigm was used, and, conditioning score and locomotor activity were recorded by Ethovision software. The results showed that unilateral intra-VTA administration of orexin A (27, 53 and 107 ng/0.3 µl saline) during conditioning phase induced CPP in a dose-dependent manner. The most effective dose of intra-VTA orexin-A in eliciting CPP was 107 ng. However, intra-NAc administration of SCH 23390 (0.25, 1 and 4 µg/0.5 µl saline), a D1 receptor antagonist, and sulpiride (0.25, 1 and 4 µg/0.5 µl DMSO), a D2 receptor antagonist, inhibited the development of orexin-induced CPP. The inhibitory effect of D2 but not D1 receptor antagonist was exerted in a dose-dependent manner. It is supposed that the activation of VTA dopaminergic neuron by orexin impresses the D2 receptors more than D1 receptors in the NAc.

ERK and p38 inhibitors attenuate memory deficits and increase CREB phosphorylation and PGC-1α levels in Aß-injected rats.

In this study, we investigated the effect of intracerebroventricular administration of ERK and p38 specific inhibitors, U0126 and PD169316, respectively, on learning and memory deficits induced by amyloid beta (Aß) in rats. To investigate the effects of these compounds on learning and memory, we performed Morris water maze (MWM) test. U0126 and/or PD169316 improved spatial learning in MWM in Aß-injected rats, 20 days after Aß-injection. To determine the mechanisms of action of U0126 and PD169316, we studies their effect on some intracellular signaling pathways such as Ca(+)/cAMP-response element binding protein (CREB), c-fos, and transcription factors that regulate mitochondrial biogenesis. Based on our data, CREB and c-fos levels decreased 7 days after Aß-injection, while U0126 and/or PD169316 pretreatments significantly increased these levels. Moreover, U0126 and PD169316 activated peroxisome proliferator-activated receptor gamma coactivator-1a, nuclear respiratory factor 1, and mitochondrial transcription factor A, 7 days after Aß-injection. Surprisingly, these factors were returned to vehicle level, 20 days after Aß-injection. Our findings reinforce the potential neuroprotective effect of these inhibitors against the Aß toxicity.

Changes in phosphorylation of CREB, ERK, and c-fos induction in rat ventral tegmental area, hippocampus and prefrontal cortex after conditioned place preference induced by chemical stimulation of lateral hypothalamus.

Experimental evidence indicates that chemical stimulation of lateral hypothalamus (LH) by carbachol can produce conditioned place preference (CPP) in rats. Several lines of evidence have shown that cAMP-response element binding protein (CREB), extracellular signal-regulated kinase (ERK), and c-fos have pivotal role in CPP induced by drugs of abuse, such as morphine, cocaine, nicotine, and alcohol. Therefore, in the present study, we investigated the changes in phosphorylated-CREB (p-CREB) and -ERK (p-ERK), and c-fos induction within ventral tegmental area (VTA), hippocampus and prefrontal cortex (PFC) after the acquisition of CPP induced by intra-LH administration of carbachol. Animals were unilaterally implanted by cannula into LH. For chemical stimulation of LH, carbachol (250 nmol/0.5 µl saline) was microinjected once each day, during 3-day conditioning phase (acquisition period) of CPP paradigm. After the acquisition period, the brains were removed, and p-CREB and p-ERK, and c-fos induction in the ipsilateral VTA, hippocampus and PFC were measured by Western blot analysis. The results indicated a significant increase in level of phosphorylated CREB (P<0.01) in VTA, and PFC (P<0.05), during LH stimulation-induced CPP, while its level decreased in hippocampus (P<0.05). Also, in aforementioned regions, an increase in c-fos level was observed, but this enhancement in PFC was not significant. Moreover, p-ERK changed in these areas, but not significantly. Our findings suggest that studying the intracellular signals and their changes, such as phosphorylated-CREB, can elucidate a functional relationship between LH and other brain structures involved in reward processing in rats.

Chemical stimulation of the lateral hypothalamus induces conditioned place preference in rats: Involvement of OX1 and CB1 receptors in the ventral tegmental area.

Orexinergic projection originated from the lateral hypothalamus (LH) to the ventral tegmental area (VTA) has an important role in the acquisition of morphine conditioned place preference (CPP). However, little if any is known about the function and/or effect of orexin on CPP in rats. In the present study, we investigated the direct effect of orexinergic neurons on acquisition of CPP by chemical stimulation of LH and involvement of orexin-A and CB1 receptors within the VTA in development of reward-related behaviors. 129 adult male albino Wistar rats weighing 220-320 g were unilaterally implanted by two separate cannulae into the LH and VTA. The CPP paradigm was done; conditioning score and locomotor activity were recorded by Ethovision software. The results showed that unilateral intra-LH administration of carbachol (62.5, 125 and 250 nmol/0.5 µl saline) as a cholinergic agonist, during conditioning phase, induced CPP in a dose-dependent manner. The maximal effect was shown at the dose of 250 nmol (P<0.001) compared to vehicle (saline) group. However, intra-VTA administration of SB334867 as a selective orexin-A receptor antagonist (0.1, 1 and 10 nmol/0.3 µl DMSO) and AM251 (5, 25 and 125 nmol/0.3 µl DMSO) as a CB1 receptor antagonist, just 5 min before carbachol during the 3-day conditioning phase, could dose-dependently inhibit the development of LH stimulation-induced CPP in the rats. It is supposed that the orexinergic projection from LH to VTA is involved in LH chemical stimulation-induced CPP and orexin-A receptor in the VTA has a substantial role in this phenomenon. Our findings also suggest the existence of cross-talk between cannabinoid and orexinergic systems within the VTA in conditioned place preference paradigm.