M. Pala, Ismail Meral, Nilgun Pala Acikgoz, Murat Mengi, Meryem Betül Erdim Gokce, Rumeysa Unsal, Yalcin Polat, F. Akbaş, Şenay Gorucu Yilmaz
{"title":"Thymoquinone ameliorates symptoms of Parkinson's disease in a 6-OHDA rat model by downregulation of miR-204-3p.","authors":"M. Pala, Ismail Meral, Nilgun Pala Acikgoz, Murat Mengi, Meryem Betül Erdim Gokce, Rumeysa Unsal, Yalcin Polat, F. Akbaş, Şenay Gorucu Yilmaz","doi":"10.1097/FBP.0000000000000776","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000776","url":null,"abstract":"microRNAs (miRNAs) play a significant role in the pathophysiology of Parkinson's disease. In this study, we evaluated the neuroprotective effect of thymoquinone on the expression profiles of miRNA and cognitive functions in the 6-hydroxydopamine (6-OHDA)-induced Parkinson's model. Male adult Wistar albino rats (200-230 g, n = 36) were randomly assigned to six groups: Sham, thymoquinone (10 mg/kg, p.o.), 6-OHDA, 6-OHDA + thymoquinone (10 mg/kg), 6-OHDA + thymoquinone (20 mg/kg), and 6-OHDA + thymoquinone (50 mg/kg). Behavioral changes were detected using the open field and the elevated plus maze tests. The mature 728 miRNA expressions were evaluated by miRNA microarray (GeneChip miRNA 4.0). Ten miRNAs were selected (rno-miR-212-5p, rno-miR-146b-5p, rno-miR-150-5p, rno-miR-29b-2-5p, rno-miR-126a-3p, rno-miR-187-3p, rno-miR-34a-5p, rno-miR-181d-5p, rno-miR-204-3p, and rno-miR-30c-2-3p) and confirmed by real-time PCR. Striatum samples were stained with hematoxylin-eosin to determine the effect of dopaminergic lesions. One-way ANOVA test and independent sample t-test were used for statistical analyses. rno-miR-204-3p was upregulated at 6-OHDA and downregulated at the 50 mg/kg dose of thymoquinone. In conclusion, thymoquinone at a dose of 50 mg/kg ameliorates symptoms of Parkinson's disease in a 6-OHDA rat model by downregulation of miR-204-3p. Also, the results showed that thymoquinone can improve locomotor activity and willing exploration and decreased anxiety. Therefore, thymoquinone can be used as a therapeutic agent.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"21 11","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140659087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NSC689857, an inhibitor of Skp2, produces antidepressant-like effects in mice.","authors":"Qingqing Liu, Li Cheng, Fu-Gui Li, Haojie Zhu, Xu Lu, Chao Huang, Xiaomei Yuan","doi":"10.1097/FBP.0000000000000773","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000773","url":null,"abstract":"We have previously reported that two inhibitors of an E3 ligase S-phase kinase-associated protein 2 (Skp2), SMIP004 and C1, have an antidepressant-like effect in non-stressed and chronically stressed mice. This prompted us to ask whether other Skp2 inhibitors could also have an antidepressant effect. Here, we used NSC689857, another Skp2 inhibitor, to investigate this hypothesis. The results showed that administration of NSC689857 (5 mg/kg) produced an antidepressant-like effect in a time-dependent manner in non-stressed male mice, which started 8 days after drug administration. Dose-dependent analysis showed that administration of 5 and 10 mg/kg, but not 1 mg/kg, of NSC689857 produced antidepressant-like effects in both non-stressed male and female mice. Administration of NSC689857 (5 mg/kg) also induced antidepressant-like effects in non-stressed male mice when administered three times within 24 h (24, 5, and 1 h before testing) but not when administered acutely (1 h before testing). In addition, NSC689857 and fluoxetine coadministration produced additive antidepressant-like effects in non-stressed male mice. These effects of NSC689857 were not associated with the changes in locomotor activity. Administration of NSC689857 (5 mg/kg) also attenuated depression-like behaviors in male mice induced by chronic social defeat stress, suggesting therapeutic potential of NSC689857 in depression. Overall, these results suggest that NSC689857 is capable of exerting antidepressant-like effects in both non-stressed and chronically stressed mice.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"33 4","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140662723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prior cocaine self-administration does not impair the ability to delay gratification in rats during diminishing returns.","authors":"H. Pribut, N. Kang, M. Roesch","doi":"10.1097/FBP.0000000000000771","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000771","url":null,"abstract":"Previous exposure to drugs of abuse produces impairments in studies of reversal learning, delay discounting and response inhibition tasks. While these studies contribute to the understanding of normal decision-making and how it is impaired by drugs of abuse, they do not fully capture how decision-making impacts the ability to delay gratification for greater long-term benefit. To address this issue, we used a diminishing returns task to study decision-making in rats that had previously self-administered cocaine. This task was designed to test the ability of the rat to choose to delay gratification in the short-term to obtain more reward over the course of the entire behavioral session. Rats were presented with two choices. One choice had a fixed amount of time delay needed to obtain reward [i.e. fixed delay (FD)], while the other choice had a progressive delay (PD) that started at 0 s and progressively increased by 1 s each time the PD option was selected. During the 'reset' variation of the task, rats could choose the FD option to reset the time delay associated with the PD option. Consistent with previous results, we found that prior cocaine exposure reduced rats' overall preference for the PD option in post-task reversal testing during 'no-reset' sessions, suggesting that cocaine exposure made rats more sensitive to the increasing delay of the PD option. Surprisingly, however, we found that rats that had self-administered cocaine 1-month prior, adapted behavior during 'reset' sessions by delaying gratification to obtain more reward in the long run similar to control rats.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"35 7","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140660564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chronic caffeine decreases anxiety-like behavior in the marble burying task in adolescent rats.","authors":"Gwi Park, Sarah M Turgeon","doi":"10.1097/FBP.0000000000000777","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000777","url":null,"abstract":"Exposure to chronic caffeine during adolescence has been shown to produce decreased anxiety-like behaviors in rats as well as decreased immobility in the forced swim test (FST) suggesting an antidepressant-like effect. The effects of chronic caffeine on anxiety, however, have been found to be test-dependent and sexually dimorphic. In addition, decreased immobility in the FST has been argued to reflect a shift toward active coping behavior as opposed to an antidepressant-like effect. In order to further characterize the effects of adolescent caffeine exposure, the present experiment assessed the effects of caffeine on marble burying behavior in a two-zone marble burying task. There was no difference in the amount of time rats spent in the two zones failing to support a shift in coping strategy. Caffeine-exposed rats spent less time engaged in marble burying activity and buried slightly fewer marbles, suggesting an anxiolytic effect of caffeine. In addition, caffeine treated rats spent less time engaged in nondirected burying and slightly more time actively engaging with the marbles; however, these effects appeared to be sexually dimorphic as they were driven by larger changes in the females. Overall, these results support an anxiolytic effect of adolescent caffeine, with female behavior appearing to be more affected by caffeine than males.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"40 15","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140662834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huijun Liu, Tao Zhu, Linlin Zhang, Fu-Gui Li, Meng Zheng, Bingran Chen, Haojie Zhu, Jie Ren, Xu Lu, Chao Huang
{"title":"Immunization with a low dose of zymosan A confers resistance to depression-like behavior and neuroinflammatory responses in chronically stressed mice.","authors":"Huijun Liu, Tao Zhu, Linlin Zhang, Fu-Gui Li, Meng Zheng, Bingran Chen, Haojie Zhu, Jie Ren, Xu Lu, Chao Huang","doi":"10.1097/FBP.0000000000000774","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000774","url":null,"abstract":"Stimulation of the innate immune system prior to stress exposure is a possible strategy to prevent depression under stressful conditions. Based on the innate immune system stimulating activities of zymosan A, we hypothesize that zymosan A may prevent the development of chronic stress-induced depression-like behavior. Our results showed that a single injection of zymosan A 1 day before stress exposure at a dose of 2 or 4 mg/kg, but not at a dose of 1 mg/kg, prevented the development of depression-like behaviors in mice treated with chronic social defeat stress (CSDS). The prophylactic effect of a single zymosan A injection (2 mg/kg) on CSDS-induced depression-like behaviors disappeared when the time interval between zymosan A and stress exposure was extended from 1 day or 5 days to 10 days, which was rescued by a second zymosan A injection 10 days after the first zymosan A injection and 4 days (4×, once daily) of zymosan A injections 10 days before stress exposure. Further analysis showed that a single zymosan A injection (2 mg/kg) 1 day before stress exposure could prevent the CSDS-induced increase in pro-inflammatory cytokines in the hippocampus and prefrontal cortex. Inhibition of the innate immune system by pretreatment with minocycline (40 mg/kg) abolished the preventive effect of zymosan A on CSDS-induced depression-like behaviors and CSDS-induced increase in pro-inflammatory cytokines in the brain. These results suggest that activation of the innate immune system triggered by zymosan A prevents the depression-like behaviors and neuroinflammatory responses in the brain induced by chronic stress.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"47 3","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140663219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Z. Kolokotroni, Therese E Fozard, D. L. Selby, Amanda A. Harrison
{"title":"Is impulsivity related to attentional bias in cigarette smokers? An exploration across levels of nicotine dependency and deprivation.","authors":"K. Z. Kolokotroni, Therese E Fozard, D. L. Selby, Amanda A. Harrison","doi":"10.1097/FBP.0000000000000775","DOIUrl":"https://doi.org/10.1097/FBP.0000000000000775","url":null,"abstract":"Research has largely focused on how attentional bias to smoking-related cues and impulsivity independently influence the development and maintenance of cigarette smoking, with limited exploration of the relationship between these mechanisms. The current experiments systematically assessed relationships between multiple dimensions of impulsivity and attentional bias, at different stages of attention, in smokers varying in nicotine dependency and deprivation. Nonsmokers (NS; n = 26), light-satiated smokers (LS; n = 25), heavy-satiated smokers (HS; n = 23) and heavy 12-hour nicotine-deprived smokers (HD; n = 30) completed the Barratt Impulsivity Scale, delayed discounting task, stop-signal task, information sampling task and a visual dot-probe assessing initial orientation (200 ms) and sustained attention (2000 ms) toward smoking-related cues. Sustained attention to smoking-related cues was present in both HS and LS, while initial orientation bias was only evident in HS. HS and LS also had greater levels of trait motor and nonplanning impulsivity and heightened impulsive choice on the delay discounting task compared with NS, while heightened trait attentional impulsivity was only found in HS. In contrast, in HD, nicotine withdrawal was associated with no attentional bias but heightened reflection impulsivity, poorer inhibitory control and significantly lower levels of impulsive choice relative to satiated smokers. Trait and behavioral impulsivity were not related to the extent of attentional bias to smoking-related cues at any stage of attention, level of nicotine dependency or state of deprivation. Findings have both clinical and theoretical implications, highlighting the unique and independent roles impulsivity and attentional bias may play at different stages of the nicotine addiction cycle.","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"32 12","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140677424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Behavioural PharmacologyPub Date : 2024-04-01Epub Date: 2024-02-23DOI: 10.1097/FBP.0000000000000763
Mohammad Nikoohemmat, Danial Farmani, Seyed Mohammadmisagh Moteshakereh, Sakineh Salehi, Laleh Rezaee, Abbas Haghparast
{"title":"Intra-accumbal orexinergic system contributes to the stress-induced antinociceptive behaviors in the animal model of acute pain in rats.","authors":"Mohammad Nikoohemmat, Danial Farmani, Seyed Mohammadmisagh Moteshakereh, Sakineh Salehi, Laleh Rezaee, Abbas Haghparast","doi":"10.1097/FBP.0000000000000763","DOIUrl":"10.1097/FBP.0000000000000763","url":null,"abstract":"<p><p>Stress and pain are interleaved at numerous levels - influencing each other. Stress can increase the nociception threshold in animals, long-known as stress-induced analgesia (SIA). Orexin is known as a neuropeptide that modulates pain. The effect of stress on the mesolimbic system in the modulation of pain is known. The role of the intra-accumbal orexin receptors in the modulation of acute pain by forced swim stress (FSS) is unclear. In this study, 117 adult male albino Wistar rats (270-300 g) were used. The animals were unilaterally implanted with cannulae above the NAc. The antagonist of the orexin-1 receptor (OX1r), SB334867, and antagonist of the orexin-2 receptor (OX2r), TCS OX2 29, were microinjected into the NAc in different doses (1, 3, 10, and 30 nmol/0.5 µl DMSO) before exposure to FSS for a 6-min period. The tail-flick test was carried out as an assay nociception of acute pain, and the nociceptive threshold [tail-flick latency (TFL)] was measured for 60-minute. The findings demonstrated that exposure to acute stress could remarkably increase the TFLs and antinociceptive responses. Moreover, intra-accumbal microinjection of SB334867 or TCS OX2 29 blocked the antinociceptive effect of stress in the tail-flick test. The contribution of orexin receptors was almost equally modulating SIA. The present study's findings suggest that OX1r and OX2r within the NAc modulate stress-induced antinociceptive responses. The intra-accumbal microinjection of orexin receptors antagonists declares inducing antinociceptive responses by FSS in acute pain. Proposedly, intra-accumbla orexinergic receptors have a role in the development of SIA.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"92-102"},"PeriodicalIF":1.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuronal nicotinic acetylcholine receptor of the central amygdala modulates the ethanol-induced tolerance to anxiolysis and withdrawal-induced anxiety in male rats.","authors":"Antariksha Duratkar, Richa Patel, Nishant Sudhir Jain","doi":"10.1097/FBP.0000000000000770","DOIUrl":"10.1097/FBP.0000000000000770","url":null,"abstract":"<p><p>The nicotine acetylcholinergic receptor (nAchR) in the central nucleus of the amygdala (CeA) is known to modulate anxiety traits as well as ethanol-induced behavioral effects. Therefore, the present study investigated the role of CeA nAChR in the tolerance to ethanol anxiolysis and withdrawal-induced anxiety-related effects in rats on elevated plus maze (EPM). To develop ethanol dependence, rats were given free access to an ethanol-containing liquid diet for 10 days. To assess the development of tolerance, separate groups of rats were challenged with ethanol (2 g/kg, i.p.) on days 1, 3, 5, 7 and 10 during the period of ethanol exposure, followed by an EPM assessment. Moreover, expression of ethanol withdrawal was induced after switching ethanol-dependent rats to a liquid diet on day 11, and withdrawal-induced anxiety-like behavior was noted at different post-withdrawal time points using the EPM test. The ethanol-dependent rats were pretreated with intra-CeA (i.CeA) (bilateral) injections of nicotine (0.25 µg/rat) or mecamylamine (MEC) (5 ng/rat) before the challenge dose of ethanol on subthreshold tolerance on the 5th day or on peak tolerance day, that is, 7th or 10th, and before assessment of postwithdrawal anxiety on the 11th day on EPM. Bilateral i.CeA preadministration of nicotine before the challenge dose of ethanol on days 5, 7 and 10 exhibited enhanced tolerance, while injection of MEC, completely mitigated the tolerance to the ethanol-induced antianxiety effect. On the other hand, ethanol-withdrawn rats pretreated i.CeA with nicotine exacerbated while pretreatment with MEC, alleviated the ethanol withdrawal-induced anxiety on all time points. Thus, the present investigation indicates that stimulation of nAChR in CeA negatively modulates the ethanol-induced chronic behavioral effects on anxiety in rats. It is proposed that nAChR antagonists might be useful in the treatment of alcohol use disorder and ethanol withdrawal-related anxiety-like behavior.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"35 2-3","pages":"132-146"},"PeriodicalIF":1.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Behavioural PharmacologyPub Date : 2024-04-01Epub Date: 2023-08-15DOI: 10.1097/FBP.0000000000000746
Azam Notaj, Amir Erfanparast, Esmaeal Tamaddonfard, Farhad Soltanalinejad-Taghiabad
{"title":"Exogenous histamine and H 2 receptor activation and H 3 receptor inhibition in nucleus accumbens modulate formalin-induced orofacial nociception through opioid receptors.","authors":"Azam Notaj, Amir Erfanparast, Esmaeal Tamaddonfard, Farhad Soltanalinejad-Taghiabad","doi":"10.1097/FBP.0000000000000746","DOIUrl":"10.1097/FBP.0000000000000746","url":null,"abstract":"<p><p>It has been demonstrated that the nucleus accumbens (NAc) plays an important role in modulation of nociception due to its extensive connections with different regions of the brain. In addition, this nucleus receives histaminergic projections from tuberomammillary nucleus. Considering the role of the central histaminergic system in nociception, the effect of histamine and its H 2 and H 3 receptors agonist and antagonist microinjections into the NAc on orofacial formalin nociception was investigated. In male Wistar rats, using stereotaxic surgery, two guide cannulas were bilaterally implanted into the right and left sides of the NAc. Diluted formalin solution (1.5%, 50 µl) injection into the vibrissa pad led to orofacial nociception. Immediately after injection, face rubbing was observed at 3-min blocks for 45 min. Orofacial formalin nociception was characterized by a biphasic nociceptive response (first phase: 0-3 min and second phase: 15-33 min). Microinjections of histamine (0.5 and 1 μg/site), dimaprit (1 μg/site, H 2 receptor agonist) and thioperamide (2 μg/site, H 3 receptor antagonist) attenuated both phases of formalin orofacial nociception. Prior microinjection of famotidine (2 μg/site) inhibited the antinociceptive effects of dimaprit (1 μg/site). Furthermore, comicroinjection of thioperamide (2 μg/site) and immepip (1 μg/site) prevented thioperamide (2 μg/site)-induced antinociception. Naloxone (2 μg/site) also prevented histamine, dimaprit- and thioperamide-induced antinociception. The results of this study demonstrate that at the level of the NAc, histamine and its H 2 and H 3 receptors are probably involved in the modulation of orofacial nociception with an opioid system-dependent mechanism.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":" ","pages":"66-78"},"PeriodicalIF":1.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9988470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Behavioural PharmacologyPub Date : 2024-04-01Epub Date: 2024-03-06DOI: 10.1097/FBP.0000000000000764
Nicholas R Mill, Richard H Ogoe, Nazanin Valibeigi, Diyi Chen, Carmen L Kimbal, Stanley J Yoon, Shaunak Ganju, Josue A Perdomo, Anjali Sardana, Daniel G McHail, Diego A Gonzalez, Theodore C Dumas
{"title":"Positive modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors differentially alters spatial learning and memory in juvenile rats younger and older than three weeks.","authors":"Nicholas R Mill, Richard H Ogoe, Nazanin Valibeigi, Diyi Chen, Carmen L Kimbal, Stanley J Yoon, Shaunak Ganju, Josue A Perdomo, Anjali Sardana, Daniel G McHail, Diego A Gonzalez, Theodore C Dumas","doi":"10.1097/FBP.0000000000000764","DOIUrl":"10.1097/FBP.0000000000000764","url":null,"abstract":"<p><p>Remarkable performance improvements occur at the end of the third postnatal week in rodents tested in various tasks that require navigation according to spatial context. While alterations in hippocampal function at least partially subserve this cognitive advancement, physiological explanations remain incomplete. Previously, we discovered that developmental modifications to hippocampal glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in juvenile rats was related to more mature spontaneous alternation behavior in a symmetrical Y-maze. Moreover, a positive allosteric modulator of AMPA receptors enabled immature rats to alternate at rates seen in older animals, suggesting an excitatory synaptic limitation to hippocampal maturation. We then validated the Barnes maze for juvenile rats in order to test the effects of positive AMPA receptor modulation on a goal-directed spatial memory task. Here we report the effects of the AMPA receptor modulator, CX614, on spatial learning and memory in the Barnes maze. Similar to our prior report, animals just over 3 weeks of age display substantial improvements in learning and memory performance parameters compared to animals just under 3 weeks of age. A moderate dose of CX614 enabled immature animals to move more directly to the goal location, but only after 1 day of training. This performance improvement was observed on the second day of training with drug delivery or during a memory probe trial performed without drug delivery after the second day of training. Higher doses created more search errors, especially in more mature animals. Overall, CX614 provided modest performance benefits for immature rats in a goal-directed spatial memory task.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"35 2-3","pages":"79-91"},"PeriodicalIF":1.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10921984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}