Endoscopic endonasal resection of symptomatic Rathke's cleft cysts: outcomes of the strategy to maintain the fenestration open.

PURPOSE: The study intends to clarify the optimal endoscopic endonasal surgical strategy for symptomatic Rathke's cleft cysts (RCCs). METHODS: We retrospectively analyzed patients with RCCs that underwent EEA surgery. The strategy for surgical and reconstruction method selection was presented. Patients were split into groups of fenestration open or closed. Pre- and postoperative symptoms, imaging, ophthalmologic, and endocrinologic exams were reviewed. The incidence of complications and the recurrence rates were determined. RESULTS: The 75 individuals were all received primary operations. The fenestration closed group contained 32 cases, while the fenestration open group contained 43 cases. The median follow-up period was 39 months. The three primary complaints were headache (n = 51, 68.00%), vision impairment (n = 45, 60.00%), and pituitary dysfunction (n = 16, 21.33%). Of the 51 patients with preoperative headaches, 48 (94.12%) reported improvement in their symptoms following surgery. Twenty-three out of 45 patients (51.11%) experienced an improvement in visual impairment. Pituitary dysfunction was found improved in 14 out of 16 individuals (87.50%). There was no discernible difference in the rate of symptom alleviation between both groups. There were three patients (3/75, 4.00%) had cyst reaccumulation. One of them (1/75, 1.33%), which needed reoperation, was healed using pterional approach. In term of complications, cerebral infections occurred in two patients (2/75, 2.67%). Both of them recovered after antibiotic treatment. No postoperative cerebrospinal fluid rhinorrhea occurred. One patient (1/75, 1.33%) in the open group experienced epistaxis. There was no persistent hypopituitarism or diabetes insipidus (DI). Analysis of headache related factors showed that the presence of wax like nodules was related to it. CONCLUSION: RCC was successfully treated with endoscopic endonasal surgery with few problems when the fenestration was kept as open as feasible. Preoperative identification of T2WI hypointense nodules may be a potential reference factor for surgical indication.

Predicting Subtype of Growth Hormone Pituitary Adenoma based on Magnetic Resonance Imaging Characteristics.

PURPOSE: This study aimed to investigate the value of magnetic resonance (MR) characteristics in differentiating the subtypes of growth hormone pituitary adenomas. MATERIALS AND METHODS: The clinical and MR imaging data of 70 patients with growth hormone pituitary adenoma confirmed by surgery and pathology were retrospectively analyzed. The tumors were divided into dense granular (DG; 36 cases) and sparse granular subtypes (SG; 34 cases). The tumors' MR features were analyzed, including the mean and maximum diameters, T2 signal intensity, T2 relative signal intensity (rSI), homogeneity, enhancement degree, and invasiveness (Knosp grade). Mann-Whitney U test and χ2 test were used to analyze MR characteristics between the 2 groups. The independent predictors and predictive probabilities of tumor subtypes were obtained via a logistic regression model, and the efficacy was compared by receiver operating characteristic curve. RESULTS: The mean and maximum diameters of growth hormone adenoma in DG and SG were 1.77 versus 2.45 and 1.95 versus 3.00 cm (median, P < 0.05), respectively. There was a significant difference between the 2 groups in T2 signal intensity and rSI (P values were 0.02 and 0.001, respectively). Most DG adenomas (86.1%) appeared as hypointense on T2 images, and 38.2% of SG adenomas were hyperintense. There was no significant difference in tumor homogeneity (P = 0.622). A significant difference was found in the Knosp grade between the 2 subtypes (P = 0.004). In addition, the enhancement degree of SG adenomas was significantly higher than that of DG adenomas (P = 0.001). Logistic regression analysis showed that high T2 rSI value and marked contrast enhancement were independent predictors of the 2 subtypes, and the odds ratios were 4.811 and 4.649, respectively. The multivariate logistic model obtained relatively high predicting efficacy, and the area under the curve, sensitivity, and specificity were 0.765, 0.882, and 0.500, respectively. CONCLUSIONS: There are significant differences in tumor size, T2 signal intensity, T2 rSI, enhancement degree, and invasiveness between DG and SG adenomas. The logistic model based on the marked contrast enhancement and high T2 rSI value has an important value in predicting the subtype of growth hormone adenoma.

Densely granulated adenoma pattern is associated with an increased risk of obstructive sleep apnea in patients with acromegaly.

OBJECTIVES: To explore the prevalence of obstructive sleep apnea (OSA) and the association between the adenoma granulation patterns and OSA in patients with acromegaly. METHODS: An overnight polysomnography (PSG) assessment was carried out on participants with acromegaly. Results classified participants into a non-OSA group, mild to moderate OSA group, and severe OSA group. Morphological and biochemical analyses were performed. Demographic, clinical, biochemical, and polysomnographic data were compared among the three groups. Using logistic regression models, the risk of OSA in acromegalic subjects was estimated. RESULTS: OSA was reported in 36 of 49 patients (74%) with acromegaly. Contrasted with the non-OSA group, OSA patients had a larger proportion of the densely granulated (DG) pattern. The OSA groups with DG acromegaly had a smaller maximum tumor diameter and Vol/2 than those with the sparsely granulated (SG) pattern. Furthermore, a higher growth hormone (GH) level (45.0 ± 36.9 vs 18.6 ± 15.8, P = 0.047) and GH index (28.4 ± 13.8 vs 6.6 ± 8.2, P = 0.003) were found in DG acromegaly patients with severe OSA. Additionally, there was a trend toward higher standardized insulin-like growth factor 1 (IGF-1) in patients with DG acromegaly than in those with SG acromegaly in the severe OSA group. After adjusting for potential confounding variables, the DG pattern was correlated with the risk of OSA (OR = 14.84, 95%CI 1.36-162.20, P = 0.027) in patients with acromegaly. CONCLUSIONS: The findings indicate that a high prevalence of OSA exists in patients with acromegaly, and the DG pattern may be a risk factor for OSA in acromegaly.

Pretreating cavernous sinus with hemostatic agent injection molding during endoscopic endonasal pituitary surgery: technical note.

OBJECTIVE: To clarify the technical pearls of cavernous sinus molding technique with hemostatic agent injection during endoscopic endonasal pituitary surgery. METHODS: All patients pretreated with cavernous sinus hemostatic agent injection molding technique for hemostasis in endoscopic endonasal surgery for pituitary adenoma resection between November 2017 and June 2021 were included. A small incision was made in the cavernous sinus wall before intracavernous manipulation. The hemostatic agent was injected with gentle pressure. It spread along the venous channels and established partial molding of the cavernous sinus. Intraoperative bleeding, surgical field score, and complications were evaluated. RESULTS: Thirty-eight patients with pituitary adenoma requiring cavernous sinus manipulation were pretreated with this technique. Technically, the tailored thin blunt metal tube with its 1 cm head end bended up 45° were the best instrument to accomplish injection. Multi-spot injections were preferred to control different compartments of the cavernous sinus, which both had a better effect in bleeding control and helped to reduce the influence of trigemino-cardiac reflex. Postoperative complications, including temporal lobe edema, hemorrhage, and exophthalmos were not observed. CONCLUSION: Pretreating cavernous sinus with hemostatic agent injection molding technique during endoscopic endonasal pituitary surgery is a practical, effective and safe method for intracavernous bleeding control.

Preoperative prediction of granulation pattern subtypes in GH-secreting pituitary adenomas.

OBJECTIVE: The aim of this study was to establish a preoperative prediction method for sparsely granulated (SG) growth hormone (GH)-secreting pituitary adenoma, an aggressive tumour subtype with high recurrence risk, in acromegaly patients. METHODS: Eighty-three patients with GH-secreting pituitary adenomas were included in this study. GH measurements, cytokeratin immunostaining and electron microscopy were performed to detect granulation patterns. Preoperative factors, including general, radiological and endocrinological features and acute octreotide suppression test outcomes, were compared between SG and densely granulated (DG) groups. The predictive capabilities of these features were analysed using a receiver operating characteristic (ROC) curve, and the most predictive features were combined to establish a grading scale. RESULTS: Thirty-nine of the 83 patients had SG GH-secreting pituitary adenomas; 44 had DG tumours. SG tumours tended to occur in younger patients and have larger diameters and volumes, higher Knosp grades, lower GH indexes and normalized insulin-like growth factor-1 (IGF-1) level, and a lower ∆GH% after octreotide treatment. The tumour size, Knosp grade, GH index and ∆GH% after octreotide treatment had good predictive performance, with area under the curve (AUC) values ranging from 0.70 to 0.80. Combining four parameters, including diameter, Knosp grade, GH index and ∆GH% after octreotide treatment, we established a grading scale for predicting SG GH-secreting pituitary adenomas with an AUC of 0.84 and relatively high sensitivity and specificity. CONCLUSIONS: We propose a predictive method for distinguishing SG and DG GH-secreting pituitary adenomas preoperatively. This method will help physicians identify candidates for presurgical medical treatment and neurosurgeons determine radical surgical strategies for high-risk tumours.

Cross-reinforcing suturing and intranasal knotting for dural defect reconstruction during endoscopic endonasal skull base surgery.

BACKGROUND: With technical improvement, accumulating lesions could be resected using endoscopic endonasal surgery. However, cerebrospinal fluid leakage is still a concern. Intraoperative dural defect reconstruction is critical. METHOD: We developed a new knotting technique for dural closure during endoscopic skull base surgery. We presented a step-by-step description of the fascia lata inlay and autologous dural patch intermittent suturing method following cross-reinforcing principles and emphasized the key points of the novel intranasal knotting technique. CONCLUSION: The new intranasal knotting and suturing technique is a feasible method to close the dura and to prevent cerebrospinal fluid leakage.

Risk factors for postoperative intracranial infections in patients with pituitary adenoma after endoscopic endonasal transsphenoidal surgery: pneumocephalus deserves further study.

OBJECTIVE: The authors sought to identify the relevance between pneumocephalus and postoperative intracranial infections, as well as bacteriological characteristics and risk factors for intracranial infections, in patients with pituitary adenomas after endoscopic endonasal transsphenoidal surgery. METHODS: In total, data from 251 consecutive patients with pituitary adenomas who underwent pure endoscopic endonasal transsphenoidal surgeries from 2014 to 2018 were reviewed for preoperative comorbidities, intraoperative techniques, and postoperative care. RESULTS: This retrospective study found 18 cases of postoperative pneumocephalus (7.17%), 9 CNS infections (3.59%), and 12 CSF leaks (4.78%). Of the patients with pneumocephalus, 5 (27.8%) had CNS infections. In patients with CNS infections, the culture results were positive in 7 cases and negative in 2 cases. The statistical analysis suggested that pneumocephalus (maximum bubble diameter of ≥ 1 cm), diaphragmatic defects (intraoperative CSF leak, Kelly grade ≥ 1), and a postoperative CSF leak are risk factors for postoperative CNS infections. CONCLUSIONS: In pituitary adenoma patients who underwent pure endoscopic endonasal transsphenoidal surgeries, intraoperative saddle reconstruction has a crucial role for patients with postoperative intracranial infections. Additionally, postoperative pneumocephalus plays an important role in predicting intracranial infections that must not be neglected. Therefore, neurosurgeons should pay close attention to the discovery of postoperative intracranial pneumocephalus because this factor is as important as a postoperative CSF leak. Pneumocephalus (maximum bubble diameter of ≥ 1 cm), diaphragmatic defects (an intraoperative CSF leak, Kelly grade ≥ 1), and a postoperative CSF leak were risk factors predictive of postoperative intracranial infections. In addition, it is essential that operative procedures be carefully performed to avoid diaphragmatic defects, to reduce exposure to the external environment, and to decrease patients' suffering.

Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving.

Relapse to cocaine use after prolonged abstinence is an important clinical problem. This relapse is often induced by exposure to cues associated with cocaine use. To account for the persistent propensity for relapse, it has been suggested that cue-induced cocaine craving increases over the first several weeks of abstinence and remains high for extended periods. We and others identified an analogous phenomenon in rats that was termed 'incubation of cocaine craving': time-dependent increases in cue-induced cocaine-seeking over the first months after withdrawal from self-administered cocaine. Cocaine-seeking requires the activation of glutamate projections that excite receptors for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the nucleus accumbens. Here we show that the number of synaptic AMPA receptors in the accumbens is increased after prolonged withdrawal from cocaine self-administration by the addition of new AMPA receptors lacking glutamate receptor 2 (GluR2). Furthermore, we show that these new receptors mediate the incubation of cocaine craving. Our results indicate that GluR2-lacking AMPA receptors could be a new target for drug development for the treatment of cocaine addiction. We propose that after prolonged withdrawal from cocaine, increased numbers of synaptic AMPA receptors combined with the higher conductance of GluR2-lacking AMPA receptors causes increased reactivity of accumbens neurons to cocaine-related cues, leading to an intensification of drug craving and relapse.

Endoscopic Endonasal Transcavernous Transoculomotor Triangle Approach for the Resection of a Knosp 4 Pituitary Adenoma.

Objectives The current video presents the nuances of the endoscopic endonasal transcavernous transoculomotor triangle approach for the resection of a Knosp 4 pituitary adenoma protruding through the superior wall of left cavernous sinus. Design The video analyzes the clinical presentation, preoperative workup, and imaging, surgical steps and technical nuances of the surgery, the clinical outcome, and follow-up imaging. Setting The patient was treated by a skull base team with bimanual, three- to four-handed endoscopic technique. Participants The patient was a 54-year-old male with a Knosp 4 prolactinoma presented with headaches and blurred vision in both eyes for 3 weeks. He was managed with endoscopic surgery due to his preference of surgery as a rapid primary therapy to relieve mental stress of an invasive brain tumor after awareness of all therapeutic options, including the preoperative medical treatment. Main Outcome Measures The main outcome was measured in the following aspects, including the resection extent, the symptoms improvement, the radiological and endocrinological follow-up results, as well as the postoperative course of complications. Results Nearly gross total resection was achieved with one-stage endoscopic surgery. The patient recovered well with improved headaches. Postop oculomotor deficit was recovered in 2 months. Endocrinological remission was kept for 12 months with one pill of bromocriptine daily. Conclusion The endoscopic endonasal transcavernous transoculomotor triangle approach is an appropriate option for resecting Knosp 4 pituitary tumors with intracranial extension through the roof of cavernous sinus at one stage. The link to the video can be found at https://youtu.be/-YJ2PKP9voY .

Primary collision tumors of the sellar region: Experience from a single center.

Collision tumors are extremely rare in the sellar region, and their features have not been fully characterized. Here, we report our single-center experience in the diagnosis and management of these tumors, focusing primarily on their clinicopathological features. We first performed a retrospective study of pathological reports from patients who had undergone surgery for pituitary adenoma (PA) or craniopharyngioma (CP) at our hospital. Next, to identify collision tumors, patients with a second pathological diagnosis-such as Rathke's cleft cyst (RCC), gangliocytoma (GC), meningioma, or atypical teratoid/rhabdoid tumor (AT/RT)-were considered. Finally, the clinicopathological characteristics of these tumors were reviewed and analyzed. The results demonstrated that eleven of 2359 PA or CP cases (0.47 %) were found to exhibit sellar collision tumors; the patient cohort had a median age of 52 years (23-71) and was predominantly female (63.6 %, 7/11). In details, of the 2092 cases of PA, 10 were diagnosed with concurrent lesions (seven of RCC and one each of CP, meningioma, and GC). Of the 267 CP cases, a single patient presented with associated AT/RT. To our knowledge, this is the first reported adult case of this subtype. Notably, the preoperative CT and/or MRI of each patient revealed solely PA or CP. The endoscopic endonasal approach was the preferred surgery. In conclusion, the sellar collision tumors occur with low incidence, and the primary subtype is PA and RCC. Their definitive diagnosis depends primarily on pathological findings.

Differential developmental trajectories for CB1 cannabinoid receptor expression in limbic/associative and sensorimotor cortical areas.

Cannabis use during adolescence is associated with an increased risk for schizophrenia and other disorders. The neuronal basis is unclear, but prefrontal cortical mechanisms have been implicated. Here, we investigated developmental changes in the endocannabinoid system by assessing expression and function of the CB1 cannabinoid receptor in prefrontal and other cortical areas in juvenile (postnatal day 25, P25), adolescent (P40), and adult (P70) rats. Overall, the expression of CB1 receptors in the cortex is highest in juveniles and drops thereafter toward adult levels. However, CB1 receptor expression follows distinct developmental trajectories in different cortical areas. The most pronounced and progressive decrease in CB1 expression was observed in medial prefrontal and other limbic/associative regions. In contrast, major changes in sensorimotor cortices occurred only after P40. We also assessed electrophysiological measures of CB1 receptor function and found that CB1-dependent inhibition of synaptic transmission in the prefrontal cortex follows the same developmental trajectory as observed for receptor expression. Together, these findings indicate that CB1 receptor-mediated signaling decreases during development but is differentially regulated in limbic/associative vs. sensorimotor systems. Therefore, cannabis use during adolescence likely differentially affects limbic/associative and sensorimotor cortical circuits.

Usefulness of the Texture Signatures Based on Multiparametric MRI in Predicting Growth Hormone Pituitary Adenoma Subtypes.

OBJECTIVE: To explore the usefulness of texture signatures based on multiparametric magnetic resonance imaging (MRI) in predicting the subtypes of growth hormone (GH) pituitary adenoma (PA). METHODS: Forty-nine patients with GH-secreting PA confirmed by the pathological analysis were included in this retrospective study. Texture parameters based on T1-, T2-, and contrast-enhanced T1-weighted images (T1C) were extracted and compared for differences between densely granulated (DG) and sparsely granulated (SG) somatotroph adenoma by using two segmentation methods [region of interest 1 (ROI1), excluding the cystic/necrotic portion, and ROI2, containing the whole tumor]. Receiver operating characteristic (ROC) curve analysis was performed to determine the differentiating efficacy. RESULTS: Among 49 included patients, 24 were DG and 25 were SG adenomas. Nine optimal texture features with significant differences between two groups were obtained from ROI1. Based on the ROC analyses, T1WI signatures from ROI1 achieved the highest diagnostic efficacy with an AUC of 0.918, the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 85.7, 72.0, 100.0, 100.0, and 77.4%, respectively, for differentiating DG from SG. Comparing with the T1WI signature, the T1C signature obtained relatively high efficacy with an AUC of 0.893. When combining the texture features of T1WI and T1C, the radiomics signature also had a good performance in differentiating the two groups with an AUC of 0.908. In addition, the performance got in all the signatures from ROI2 was lower than those in the corresponding signature from ROI1. CONCLUSION: Texture signatures based on MR images may be useful biomarkers to differentiate subtypes of GH-secreting PA patients.

Endonasal interdural pituitary transposition for resection of a posterior clinoid process enchondroma in a patient with Maffucci syndrome.

Maffucci syndrome is an extremely rare disorder characterized by benign enchondromas, skeletal deformities, and cutaneous lesions composed of abnormal blood vessels. Enchondromas rarely arise in the cranial bones. Interdural pituitary transposition is an effective way to gain access to the posterior clinoid, without affecting the function of the pituitary gland. Here, the authors present a case of a posterior clinoid process enchondroma in a patient with Maffucci syndrome. The tumor was resected via an interdural pituitary transposition fashion. Four months postoperatively, the patient's oculomotor function had recovered to normal and the function of the pituitary gland was preserved intact. The video can be found here: https://youtu.be/EYgVwVZuC4g.

Antibiotic-induced black hairy tongue: two case reports and a review of the literature.

Black hairy tongue (BHT) is characterized by a discolored, hairy tongue. We herein report two cases of BHT associated with antibacterial agents and review previous cases. In Case 1, a 17-year-old girl with a central neurocytoma was administered intravenous piperacillin-tazobactam for postoperative infection, and BHT developed 12 days later. Her symptoms resolved 8 days after she discontinued the piperacillin-tazobactam and brushed her tongue three times daily. In Case 2, a 65-year-old man was administered intravenous piperacillin-tazobactam and levofloxacin to treat multidrug-resistant Pseudomonas aeruginosa, and BHT developed 15 days later. The piperacillin-tazobactam was discontinued and the patient brushed his tongue, and the discoloration gradually subsided thereafter. However, the BHT reappeared after linezolid treatment. The patient had adverse drug reactions to both the piperacillin-tazobactam and linezolid treatments. The BHT might have been related to antibiotic use in both cases. We identified 19 cases of antibiotic-related BHT in a literature search, but none were related to piperacillin-tazobactam use. In all cases, symptoms resolved after discontinuation of the drug and brushing of the tongue. BHT may be a rare adverse effect of antibiotics. Treatment strategies include removal of the causative agents, mechanical debridement, and good oral hygiene.

Repeated morphine exposure decreased the nucleus accumbens excitability during short-term withdrawal.

It is well known that the nucleus accumbens plays an important role in drug reinforcing effect and relapse. However, the cellular neuroadaptations that take place in accumbens neurons after repeated drug exposure are still not well understood, especially for opioids. Here, we examined how nucleus accumbens neuronal excitability becomes affected in rats exposed to morphine using whole-cell patch-clamp recordings. Medium spiny neurons recorded from brain slices of repeated morphine treated rats exhibited a significant decrease in the intrinsic excitability after 3-4 days withdrawal, compared to that of neurons from saline treated animals, which was indicated by the increase of current to evoke the first spike and the decrease of spike number induced by depolarizing current steps in the morphine group. Moreover, the excitability decrease was accompanied by related membrane property changes, such as resting membrane potential hyperpolarization, input resistance, and membrane time constant decrease, inward rectification increase, and action potential duration decrease. Taken together, repeated morphine exposure and short-term withdrawal may reduce nucleus accumbens activity and output by modulating intrinsic membrane properties of its output neurons, which could be an important neuroadaptation process that mediates morphine addictive effect.

Enhanced ability of TRPV1 channels in regulating glutamatergic transmission after repeated morphine exposure in the nucleus accumbens of rat.

Glutamatergic projections to nucleus accumbens (NAc) drive drug-seeking behaviors during opioids withdrawal. Modulating glutamatergic neurotransmission provides a novel pharmacotherapeutic avenue for treatment of opioids dependence. Great deals of researches have verified that transient receptor potential vanilloid 1 (TRPV1) channels alters synaptic transmitter release and regulate neural plasticity. In the present study, whole-cell patch clamp recordings were adopted to examine the activity of TRPV1 Channels in regulating glutamate-mediated excitatory postsynaptic currents (EPSCs) in NAc of rat during morphine withdrawal for 3days and 3weeks. The data showed that the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and the amplitudes of evoked excitatory postsynaptic currents (eEPSCs) were increased during morphine withdrawal after applied with capsaicin (TRPV1 agonist). Capsaicin decreased the paired pulse ratio (PPR) and increased sEPSCs frequency but not their amplitudes suggesting a presynaptic locus of action during morphine withdrawal. All these effects were fully blocked by the TRPV1 antagonist Capsazepine. Additionally, In the presence of AM251 (CB1 receptor antagonist), depolarization-induced release of endogenous cannabinoids activated TRPV1 channels to enhance glutamatergic neurotransmission during morphine withdrawal. The functional enhancement of TRPV1 Channels in facilitating glutamatergic transmission was not recorded in dorsal striatum. Our findings demonstrate the ability of TRPV1 in regulating excitatory glutamatergic transmission is enhanced during morphine withdrawal in NAc, which would deepen our understanding of glutamatergic modulation during opioids withdrawal.

Endoscopic Endonasal Resection of a Mixed Lesion of Gangliocytoma and Nonfunctioning Pituitary Adenoma.

BACKGROUND: The coexistence of a gangliocytoma and a pituitary adenoma is a rare event that has been reported in only case reports. The knowledge of its diagnosis and treatment is extremely limited. CASE DESCRIPTION: We present a rare case of intrasellar-suprasellar gangliocytoma and nonfunctioning pituitary adenoma. The lesion was diagnosed preoperatively as a pituitary adenoma, and it was resected using the extended endoscopic endonasal approach. We could clearly observe 2 different textures inside the tumor. The main body of the tumor tissue was tough and fibrous with distinct lobular nodules distributed within it. To our knowledge, this is the first report of distinct compartments with heterogeneous consistencies in a mixed sellar gangliocytoma-adenoma. CONCLUSIONS: Our finding of the heterogeneous texture in the lesion of gangliocytoma associated with pituitary adenoma may help to uncover the pathogenesis of this rare disorder. This finding also supports the examination of intraoperative frozen sections to aid in diagnosis. We recommend maximized safe resection as a surgical strategy for the coexistent lesion of gangliocytoma and pituitary adenoma.

The endocannabinoid system regulates synaptic transmission in nucleus accumbens by increasing DAGL-α expression following short-term morphine withdrawal.

BACKGROUND AND PURPOSE: The endocannabinoid (eCB) system is involved in pathways that regulate drug addiction and eCB-mediated synaptic plasticity has been linked with addictive behaviours. Here, we investigated the molecular mechanisms underlying the changes in eCB-dependent synaptic plasticity in the nucleus accumbens core (NAcc) following short-term withdrawal from repeated morphine treatment. EXPERIMENTAL APPROACH: Conditioned place preference (CPP) was used to evaluate the rewarding effects of morphine in rats. Evoked inhibitory postsynaptic currents of medium spiny neurons in NAcc were measured using whole-cell patch-clamp recordings. Changes in depolarization-induced suppression of inhibition (DSI) in the NAcc were assessed to determine the effect of short-term morphine withdrawal on the eCB system. To identify the potential modulation mechanism of short-term morphine withdrawal on the eCB system, the expression of diacylglycerol lipase α (DGL-α) and monoacylglycerol lipase was detected by Western blot analysis. KEY RESULTS: Repeated morphine administration for 7 days induced stable CPP. Compared with the saline group, the level of DSI in the NAcc was significantly increased in rats after short-term morphine withdrawal. Furthermore, this increase in DSI coincided with a significant increase in the expression of DGL-α. CONCLUSIONS AND IMPLICATIONS: Short-term morphine withdrawal potentiates eCB modulation of inhibitory synaptic transmission in the NAcc. We also found that DGL-α expression was elevated after short-term morphine withdrawal, suggesting that the eCB 2-arachidonyl-glycerol but not anandamide mediates the increase in DSI. These findings provide useful insights into the mechanisms underlying eCB-mediated plasticity in the NAcc during drug addiction. LINKED ARTICLES: This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc.

Docosahexaenoic acid inhibits mechanical allodynia and thermal hyperalgesia in diabetic rats by decreasing the excitability of DRG neurons.

Diabetes mellitus is a common metabolic disease in human beings with characteristic symptoms of hyperglycemia, chronic inflammation and insulin resistance. One of the most common complications of early-onset diabetes mellitus is peripheral diabetic neuropathy, which is manifested either by loss of nociception or by allodynia and hyperalgesia. Dietary fatty acids, especially polyunsaturated fatty acids, have been shown the potential of anti-inflammation and modulating neuron excitability. The present study investigated the effects of docosahexaenoic acid (DHA) on the excitability of dorsal root ganglion (DRG) neurons in streptozotocin (STZ)-induced diabetes rats. The effects of DHA on the allodynia and hyperalgesia of diabetic rats were also evaluated. Dietary DHA supplementation effectively attenuated both allodynia and hyperalgesia induced by STZ injection. DHA supplementation decreased the excitability of DRG neurons by decreasing the sodium currents and increasing potassium currents, which may contribute to the effect of alleviating allodynia and hyperalgesia in diabetic rats. The results suggested that DHA might be useful as an adjuvant therapy for the prevention and treatment of painful diabetic neuropathy.

Late adolescent expression of GluN2B transmission in the prefrontal cortex is input-specific and requires postsynaptic protein kinase A and D1 dopamine receptor signaling.

BACKGROUND: Refinement of mature cognitive functions, such as working memory and decision making, typically takes place during adolescence. The acquisition of these functions is linked to the protracted development of the prefrontal cortex (PFC) and dopamine facilitation of glutamatergic transmission. However, the mechanisms that support these changes during adolescence remain elusive. METHODS: Electrophysiological recordings (in vitro and in vivo) combined with pharmacologic manipulations were employed to determine how N-methyl-D-aspartate transmission in the medial PFC changes during the adolescent transition to adulthood. The relative contribution of GluN2B transmission and its modulation by postsynaptic protein kinase A and D1 receptor signaling were determined in two distinct age groups of rats: postnatal day (P)25 to P40 and P50 to P80. RESULTS: We found that only N-methyl-D-aspartate receptor transmission onto the apical dendrite of layer V pyramidal neurons undergoes late adolescent remodeling due to a functional emergence of GluN2B function after P40. Both protein kinase A and dopamine D1 receptor signaling are required for the functional expression of GluN2B transmission and to sustain PFC plasticity in response to ventral hippocampal, but not basolateral amygdala, inputs. CONCLUSIONS: Thus, the late adolescent acquisition of GluN2B function provides a mechanism for dopamine D1-mediated regulation of PFC responses in an input-specific manner.