Hemiarthroplasty of the elbow: the effect of implant size on joint congruency.

BACKGROUND: Distal humeral hemiarthroplasty is a treatment option for elbow joint disease that predominantly affects the distal humerus, including distal humerus fractures, nonunions, and avascular necrosis. The effect of hemiarthroplasty implants on joint contact has not been reported. The purpose of this in vitro study was to quantify the effects of hemiarthroplasty and implant size on ulnohumeral joint congruency. METHODS: Five fresh frozen cadaveric upper extremities were mounted to a custom elbow testing system. Active and passive motion were performed in dependent, horizontal, varus, and valgus positions. A registration and interbone distance algorithm was used to quantify ulnohumeral joint congruency throughout elbow flexion. RESULTS: The optimally sized hemiarthroplasty implant demonstrated the greatest joint congruency with the ulna, followed by the oversized implant, then the undersized implant. Joint congruency was greater during active vs. passive flexion, indicating that the elbow joint is more reduced in active flexion than in passive flexion. CONCLUSION: This study demonstrates that undersized distal humeral hemiarthroplasty implants have the lowest joint congruency compared with an optimally sized or oversized implant.

Hemiarthroplasty of the elbow: the effect of implant size on kinematics and stability.

BACKGROUND: Distal humeral hemiarthroplasty is a treatment option for distal humeral fractures, nonunions, and avascular necrosis. The biomechanical effects, however, have not been reported. The purpose of this in vitro study was to quantify the effects of hemiarthroplasty and implant size on elbow joint kinematics. METHODS: Eight fresh-frozen cadaveric arms were mounted in an in vitro motion simulator. An electromagnetic tracking system quantified elbow kinematics. A custom distal humeral stem was implanted by use of navigation, and 3 humeral articular spools were evaluated: optimally sized, undersized, and oversized. Statistical analysis was performed with repeated-measures analysis of variance. RESULTS: Distal humeral hemiarthroplasty altered elbow kinematics, regardless of implant size. In the valgus position, the optimally sized implant resulted in a mean increase in valgus angulation of 3° ± 1° (P = .003) as compared with the osteotomy control. In the varus position, the optimal and undersized implants both resulted in significant increases in varus angulation: 3° ± 1° (P = .01) and 3° ± 1° (P = .001), respectively. The undersized implant had the greatest alteration in kinematics, whereas the oversized implant best reproduced native elbow kinematics. CONCLUSION: This study showed a small but significant alteration in elbow joint kinematics with placement of a distal humeral hemiarthroplasty implant, regardless of implant size. This could be due to errors in implant positioning and/or differences in the shape of the humeral implant relative to the native elbow. These changes in joint tracking may cause abnormal articular contact and loading, which may result in pain and cartilage degeneration over time.

An anthropometric study of the distal humerus.

BACKGROUND: The optimal articular shape for distal humeral hemiarthroplasty has not been defined because of a paucity of data quantifying the morphology of the normal distal humerus. This study defines the osseous anatomy and anatomic variability of the distal humerus using 3-dimensional imaging techniques. METHODS: Three-dimensional surface models were created from computed tomography scans obtained from 50 unpaired human cadaveric elbows. Geometric centers of the capitellum and the trochlear groove defined the anatomic flexion-extension axis. A coordinate system was created, and the distal humerus was sectioned into 100 slices along this axis. The C line was defined as the line of best fit connecting the geometric centers of each of the slices. RESULTS: The anatomic flexion-extension axis of the distal humerus was found to be an average of 1° ± 1° from the C line (range, 0°-3°) in the coronal plane and 2° ± 1° (range, 0°-7°) in the transverse plane. The average trochlear width was 22 ± 3 mm, and the average trochlear height was 18 ± 2 mm. The mean width of the capitellum was 17 ± 2 mm; the height was 23 ± 2 mm (P < .001). CONCLUSIONS: The difference in the capitellum width and height demonstrates that the capitellum is ellipsoid, not spherical. A data bank of humeral dimensions may be used for the development of future distal humeral hemiarthroplasty implants. A more anatomic implant may optimize kinematics and maximize contact area, thus minimizing contact stresses on the native ulna and radius.

A comparison of surgical delays in directly admitted versus transferred patients with hip fractures: opportunities for improvement?

BACKGROUND: The increasing incidence of hip fractures in our aging population challenges orthopedic surgeons and hospital administrators to effectively care for these patients. Many patients present to regional hospitals and are transferred to tertiary care centres for surgical management, resulting in long delays to surgery. Providing timely care may improve outcomes, as delay carries an increased risk of morbidity and mortality. METHODS: We retrospectively reviewed the cases of all patients with hip fractures treated in a single Level 1 trauma centre in Canada between 2005 and 2012. We compared quality indicators and outcomes between patients transferred from a peripheral hospital and those directly admitted to the trauma centre. RESULTS: Of the 1191 patients retrospectively reviewed, 890 met our inclusion criteria: 175 who were transferred and 715 admitted directly to the trauma centre. Transfer patients' median delay from admission to operation was 93 hours, whereas nontransfer patients waited 44 hours (p < 0.001). The delay predominantly occurred before transfer, as the patients had to wait for a bed to become available at the trauma centre. The median length of stay in hospital was 20 days for transfer patients compared with 13 days for nontransfer patients (p < 0.001). Regional policy changes enacted in 2011 decreased the median transfer delay from regional hospital to tertiary care centre from 47 to 27 hours (p = 0.005). CONCLUSION: Policy changes can have a significant impact on patient care. Prioritizing patients and expediting transfer will decrease overall mortality, reduce hospital stay and reduce the cost of hip fracture care.

CONTEXTE: L'incidence croissante des fractures de la hanche dans notre population vieillissante pose un défi aux chirurgiens orthopédistes et aux administrateurs hospitaliers qui souhaitent offrir des soins efficaces à ces patients. De nombreux patients se présentent dans des hôpitaux régionaux avant d'être transférés dans des centres de soins tertiaires pour y être opérés, ce qui retarde la chirurgie. Fournir les soins requis en temps voulu pourrait améliorer les résultats étant donné que tout retard s'accompagne d'un risque accru de morbidité et de mortalité. MÉTHODES: Nous avons effectué une revue rétrospective de tous les cas de fracture de la hanche traités dans un centre canadien de traumatologie de niveau 1 entre 2005 et 2012. Nous avons comparé les indicateurs de qualité et les résultats entre les patients transférés d'un hôpital régional et les patients admis directement au centre de traumatologie. RÉSULTATS: Parmi les 1191 cas analysés rétrospectivement, 890 répondaient à nos critères d'inclusion : 175 avaient été transférés et 715 avaient été admis directement au centre de traumatologie. Le délai médian entre l'admission et la chirurgie chez les patients transférés a été de 93 heures, alors que les patients non transférés ont attendu 44 heures (p < 0,001). Le délai est principalement survenu avant le transfert, car les patients devaient attendre qu'un lit se libère au centre de traumatologie. La durée médiane du séjour hospitalier a été de 20 jours pour les patients transférés, contre 13 jours pour les patients non transférés (p < 0,001). Les changements apportés à la politique régionale en 2011 ont abrégé de 47 à 27 heures (p = 0,005) le délai médian avant le transfert des hôpitaux régionaux vers le centre de soins tertiaires. CONCLUSION: Les changements de politiques peuvent avoir un impact significatif sur les soins aux patients. Prioriser les cas et accélérer les transferts réduiront la mortalité globale, abrégeront les séjours hospitaliers et réduiront les coûts associés au traitement des fractures de la hanche.

Factors affecting transfusion requirement after hip fracture: can we reduce the need for blood?

BACKGROUND: Hip fractures are common injuries that result in blood loss and frequently require the transfusion of blood products. We sought to identify risk factors leading to increased blood transfusion in patients presenting with hip fractures, especially those factors that are modifiable. METHODS: We retrospectively reviewed the cases of all patients who had fixation of their hip fractures between October 2005 and February 2010. The need for transfusion was correlated with potential risk factors, including age, sex, preoperative hemoglobin, fracture type, fixation method and more. RESULTS: A total of 835 patients had fixation of their hip fractures during the study period; 631 met the inclusion criteria and 249 of them (39.5%) were transfused. We found an association between need for blood transfusion and female sex (p = 0.018), lower preoperative hemoglobin (p < 0.001), fracture type (p < 0.001) and fixation method (p < 0.001). Compared with femoral neck fractures, there was a 2.37 times greater risk of blood transfusion in patients with intertrochanteric fractures (p < 0.001) and a 4.03 times greater risk in those with subtrochanteric fractures (p < 0.001). Dynamic hip screw (DHS) fixation decreased the risk of transfusion by about half compared with intramedullary nail or hemiarthroplasty. We found no association with age, delay to operation (p = 0.17) or duration of surgery (p = 0.30). CONCLUSION: The only modifiable risk factor identified was fixation method. When considering blood transfusion requirements in isolation, we suggest a potential benefit in using a DHS for intertrochanteric and femoral neck fractures amenable to DHS fixation.

CONTEXTE: La fracture de la hanche est un traumatisme fréquent, qui cause une perte sanguine et nécessite souvent la transfusion de produits sanguins. Nous avons tenté d'identifier les facteurs de risque associés à une hausse du nombre des transfusions sanguines chez des patients ayant subi une fracture de la hanche, en particulier les facteurs modifiables. MÉTHODES: Au cours d'une étude rétrospective, on a revu les cas de tous les patients chez qui on avait pratiqué une ostéosynthèse pour une fracture de la hanche survenue entre octobre 2005 et février 2010. La nécessité d'une transfusion sanguine a été associée à d'éventuels facteurs de risque, dont l'âge, le sexe, le taux d'hémoglobine préopératoire, le type de fracture, la technique d'ostéosynthèse, et d'autres facteurs encore. RÉSULTATS: Au total, 835 patients avaient subi une ostéosynthèse pour fracture de la hanche au cours de la période à l'étude; 631 satisfaisaient les critères d'inclusion à l'étude et parmi eux, 249 (39,5 %) ont reçu une transfusion sanguine. On a observé l'existence d'un lien entre la nécessité d'une transfusion sanguine et le sexe féminin (p = 0,018), une plus faible concentration d'hémoglobine préopératoire (p < 0,001), le type de fracture (p <0,001) et la technique d'ostéosynthèse (p < 0,001). Par rapport aux fractures du col fémoral, le risque de transfusion sanguine était 2,37 fois plus élevé chez les patients présentant une fracture intertrochantérienne (p < 0,001) et 4,03 fois plus élevé chez ceux présentant une fracture sous-trochantérienne (p <0,001). En utilisant une vis dynamique de hanche, le risque de transfusion sanguine a diminué d'environ 50 % par rapport à l'enclouage centromédullaire ou à l'hémiarthroplastie. Aucun lien n'a été observé avec l'âge, le délai de l'intervention chirurgicale (p = 0,17), ni avec sa durée (p = 0,30). CONCLUSION: La technique d'ostéosynthèse est l'unique facteur de risque modifiable ayant été identifié. Mais lorsqu'on évalue la nécessité d'une transfusion sanguine sans tenir compte des facteurs de risque, nos résultats semblent indiquer qu'on aurait avantage à utiliser une vis dynamique de hanche pour consolider les fractures intertrochantériennes et les fractures du col fémoral.

Δ-9-Tetrahydrocannabinol and Cannabidiol produce dissociable effects on prefrontal cortical executive function and regulation of affective behaviors.

The use of cannabis for therapeutic and recreational purposes is growing exponentially. Nevertheless, substantial questions remain concerning the potential cognitive and affective side-effects associated with cannabis exposure. In particular, the effects of specific marijuana-derived phytocannabinoids on neural regions such as the prefrontal cortex (PFC) are of concern, given the role of the PFC in both executive cognitive function and affective processing. The main biologically active phytocannabinoids, ∆-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), interact with multiple neurotransmitter systems important for these processes directly within the PFC. Considerable evidence has demonstrated that acute or chronic THC exposure may induce psychotomimetic effects, whereas CBD has been shown to produce potentially therapeutic effects for both psychosis and/or anxiety-related symptoms. Using an integrative combination of cognitive and affective behavioral pharmacological assays in rats, we report that acute intra-PFC infusions of THC produce anxiogenic effects while producing no impairments in executive function. In contrast, acute infusions of intra-PFC CBD impaired attentional set-shifting and spatial working memory, without interfering with anxiety or sociability behaviors. In contrast, intra-PFC CBD reversed the cognitive impairments induced by acute glutamatergic antagonism within the PFC, and blocked the anxiogenic properties of THC, suggesting that the therapeutic properties of CBD within the PFC may be present only during pathologically aberrant states within the PFC. Interestingly, the effects of PFC THC vs. CBD were found to be mediated through dissociable CB1 vs. 5-HT1A-dependent receptor signaling mechanisms, directly in the PFC.

Infusions of Nerve Growth Factor Into the Developing Frontal Cortex Leads to Deficits in Behavioral Flexibility and Increased Perseverance.

In the pursuit of further establishing a neurodevelopmental animal model to investigate the mechanisms underlying impaired executive function, a core and severely debilitating symptom of schizophrenia, we sought to characterize the deficits in behavioral flexibility in adult rats following neonatal infusions of nerve growth factor (NGF) into the medial part of the developing frontal cortex. Our previous studies using this neonatal frontal cortical lesion model have shown that it leads to adult-onset positive and negative symptom-like features, and several neuropathological abnormalities of schizophrenia. In the present study, we used operant conditioning-based paradigms to investigate set-shifting ability and reversal learning performance in adult rats that received infusions of NGF into the developing frontal cortex on post-natal day 1. NGF-infusion caused apoptosis of cells in the subplate layer. Adult rats that received neonatal infusions of NGF showed decreased grey matter thickness, and decreased levels of parvalbumin in prelimbic and infralimbic areas of the medial prefrontal cortex (mPFC). NGF-treated rats had difficulty completing the set-shifting and reversal learning tasks due to increased perseverance (ie, a failure to disengage from the previously-learned strategy once the rule contingencies were changed) compared to the control group. Collectively, these results identify the crucial role of the frontal cortical subplate layer in the structural and functional development of the mPFC relevant to schizophrenia. Furthermore, the present findings substantially advance the face and construct validity of this putative preclinical model of schizophrenia based on developmental disruption of the frontal cortical subplate.

Combination of behaviorally sub-effective doses of glutamate NMDA and dopamine D1 receptor antagonists impairs executive function.

Impairment of executive function is a core feature of schizophrenia. Preclinical studies indicate that injections of either N-methyl d-aspartate (NMDA) or dopamine D1 receptor blockers impair executive function. Despite the prevailing notion based on postmortem findings in schizophrenia that cortical areas have marked suppression of glutamate and dopamine, recent in vivo imaging studies suggest that abnormalities of these neurotransmitters in living patients may be quite subtle. Thus, we hypothesized that modest impairments in both glutamate and dopamine function can act synergistically to cause executive dysfunction. In the present study, we investigated the effect of combined administration of "behaviorally sub-effective" doses of NMDA and dopamine D1 receptor antagonists on executive function. An operant conditioning-based set-shifting task was used to assess behavioral flexibility in rats that were systemically injected with NMDA and dopamine D1 receptor antagonists individually or in combination prior to task performance. Separate injections of the NMDA receptor antagonist, MK-801, and the dopamine D1 receptor antagonist, SCH 23390, at low doses did not impair set-shifting; however, the combined administration of these same behaviorally sub-effective doses of the antagonists significantly impaired the performance during set-shifting without affecting learning, retrieval of the memory of the initial rule, latency of responses or the number of omissions. The combined treatment also produced an increased number of perseverative errors. Our results indicate that NMDA and D1 receptor blockade act synergistically to cause behavioral inflexibility, and as such, subtle abnormalities in glutamatergic and dopaminergic systems may act cooperatively to cause deficits in executive function.

Outcomes of After-Hours Hip Fracture Surgery.

BACKGROUND: Given single-institution studies showing trends between after-hours hip fracture surgical procedures and adverse outcomes, as well as fixation time targets that may increasingly compel after-hours operations, we investigated the relationship between after-hours hip fracture surgical procedures and adverse outcomes in a large, population-based cohort. METHODS: All Ontarians who were ≥60 years of age and underwent a hip fracture surgical procedure between April 2002 and March 2014 were eligible for study inclusion. Data were obtained from linked health administrative databases. The primary exposure was after-hours provision of surgical procedures, occurring weekday evenings between the hours of 5 P.M. and 12 A.M. or over the weekend, but not overnight (after 12 A.M. to 7 A.M.). Surgical complications up to 6 months following a hip fracture surgical procedure comprised the primary outcome. Medical complications, including mortality, up to 90 days postoperatively were also assessed. Odds ratios (ORs) were calculated using a logistic regression model that accounted for clustering at the hospital level and adjusted for patient, provider, and fracture characteristics previously shown to explain the majority of variance in hip fracture outcomes. RESULTS: During the study period, 87,647 patients underwent an isolated hip fracture surgical procedure; 51.2% of these patients had femoral neck fractures, 44.1% had intertrochanteric fractures, and 4.7% had subtrochanteric fractures. The surgical procedure occurred after hours in 59,562 patients (68.0%), and 27,240 patients (31.1%) underwent a surgical procedure during normal hours (7 A.M. to 5 P.M.). Only 845 patients (1%) underwent a surgical procedure overnight. We observed no significant relationships between timing of the surgical procedure and adverse outcomes, except for patients who had undergone an after-hours surgical procedure and had fewer inpatient surgical complications (OR, 0.90 [95% confidence interval, 0.83 to 0.99]; p = 0.01). CONCLUSIONS: Adverse outcomes following a hip fracture surgical procedure were similar whether a surgical procedure occurred during normal hours or after hours. Concerns regarding the quality of after-hours surgical procedures should not influence hip fracture prioritization policy. However, given that the great majority of hip fracture surgical procedures occurred after hours, future research should examine other potential consequences of this practice, such as financial impact and surgeon burnout. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Behavioural inflexibility in a comorbid rat model of striatal ischemic injury and mutant hAPP overexpression.

Alzheimer disease (AD) and stroke coexist and interact; yet how they interact is not sufficiently understood. Both AD and basal ganglia stroke can impair behavioural flexibility, which can be reliably modeled in rats using an established operant based set-shifting test. Transgenic Fischer 344-APP21 rats (TgF344) overexpress pathogenic human amyloid precursor protein (hAPP) but do not spontaneously develop overt pathology, hence TgF344 rats can be used to model the effect of vascular injury in the prodromal stages of Alzheimer disease. We demonstrate that the injection of endothelin-1 (ET1) into the dorsal striatum of TgF344 rats (Tg-ET1) produced an exacerbation of behavioural inflexibility with a behavioural phenotype that was distinct from saline-injected wildtype & TgF344 rats as well as ET1-injected wildtype rats (Wt-ET1). In addition to profiling the types of errors made, interpolative modeling using logistic exposure-response regression provided an informative analysis of the timing and efficiency of behavioural flexibility. During set-shifting, Tg-ET1 committed fewer perseverative errors than Wt-ET1. However, Tg-ET1 committed significantly more regressive errors and had a less efficient strategy change than all other groups. Thus, behavioural flexibility was more vulnerable to striatal ischemic injury in TgF344 rats.

Quality of Life in Bilateral Vs. Unilateral End-Stage Ankle Arthritis and Outcomes of Bilateral Vs. Unilateral Total Ankle Replacement.

BACKGROUND: We performed a retrospective cohort study to compare preoperative health-related quality of life (HRQoL) between patients with bilateral and those with unilateral end-stage ankle arthritis. We also compared midterm outcomes in a subgroup of patients who had undergone staged bilateral total ankle replacement (TAR) with the outcomes in the group treated with unilateral TAR. METHODS: The HRQoL before surgical treatment was compared between 53 patients with bilateral end-stage ankle arthritis identified from the Canadian Orthopaedic Foot and Ankle Society Prospective Ankle Reconstruction Database and 106 patients with unilateral arthritis selected from the same database. Short Form-36 (SF-36) and American Academy of Orthopaedic Surgeons Foot and Ankle Module (AAOS-FAM) scores were used to assess preoperative HRQoL. Midterm outcomes (implant survival, HRQoL, and reoperation and revision rates) were compared between 37 patients who had undergone staged bilateral TAR and 106 patients treated with unilateral TAR; all patients were followed for at least 2 years. RESULTS: Preoperatively, patients with unilateral disease had a higher prevalence of posttraumatic arthritis, whereas patients with bilateral disease had a higher prevalence of primary and secondary arthritis (p < 0.001). The mean preoperative SF-36 physical component summary (PCS) score in the unilateral group was higher than that in the bilateral group (p < 0.002). The mean postoperative follow-up (and standard deviation) was 5.0 ± 2.0 years in the bilateral TAR group and 4.0 ± 1.8 years in the unilateral TAR group. The patients who underwent either unilateral or staged bilateral TAR demonstrated improved SF-36 PCS scores between the preoperative and postoperative evaluations (p < 0.001). The postoperative SF-36 PCS scores were similar between the patients with unilateral TAR and those with bilateral TAR (p = 0.70). Six ankles (6%) in the unilateral cohort and 6 ankles (8%) in the bilateral cohort required revision of the metal component (p = 0.52). The mean implant survival time was 10.9 years (95% confidence interval [CI] = 10.1 to 11.7 years) in the bilateral cohort and 9.2 years (95% CI = 8.5 to 9.8 years) in the unilateral cohort (p = 0.60). CONCLUSIONS: Preoperative SF-36 scores demonstrated that bilateral end-stage ankle arthritis is a more debilitating condition than unilateral arthritis. Patients who underwent staged bilateral TAR benefited as much as patients who underwent unilateral TAR, despite having a worse preoperative health status. Metal component revision rates and implant survival were similar between the 2 groups. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

A simple and economical method of electrode fabrication for brain self-stimulation in rats.

INTRODUCTION: Intracranial self-stimulation (ICSS) is an operant paradigm in which rodents self-administer rewarding electrical stimulation through electrodes implanted into the brain. We describe a simple, inexpensive and reliable method to fabricate monopolar and bipolar electrodes, along with the swivel system, for delivery of electric pulses at the targeted sites in the brain of rat. METHODS: The system consists of an insulated stainless steel wire(s) (diameter: 0.25 mm), plastic base, pedestal and connector attached to a swivel via a stimulating cable, which is connected to the stimulator. We provide the specifications, source of each component, and the method of fabrication in details. RESULTS: In-house fabricated monopolar or bipolar electrodes were subjected to rigorous tests. We implanted the electrode into the medial forebrain bundle (MFB) and rat was trained to press the lever for electrical self-stimulation in operant chamber for 60 min each day. In about 3-4 days, the animal gave a consistent response (~40 presses/min) and was considered as conditioned. For evaluation of reinforcement behavior, the number of lever pressings of conditioned rat with or without electrical stimulation was assessed for a period of 30 min each day for 10 weeks. The rewarding frequency sustained for the entire duration. In addition, we compared the lever pressing data of the groups of rats implanted with in-house fabricated versus with those with commercial electrodes; no significant differences were encountered. DISCUSSION: The required components for the electrode fabrication are easily available. With some practice, the system can be easily assembled in the laboratory and costs less than a dollar. We suggest that the electrodes, fabricated using this method, may serve as an economical and reliable tool in neuropharmacological and neurobehavioral studies.

NPY mediates reward activity of morphine, via NPY Y1 receptors, in the nucleus accumbens shell.

Although the interaction between endogenous neuropeptide Y (NPY) and opioidergic systems in processing of reward has been speculated, experimental evidence is lacking. We investigated the role of NPY, and its Y1 receptors, in the nucleus accumbens shell (AcbSh) in morphine induced reward and reinforcement behavior. Rats were implanted with cannulae targeted at AcbSh for drug administration, and with stimulating electrode in the medial forebrain bundle (MFB). The rats were then conditioned in an operant conditioning chamber for electrical self-stimulation of the MFB. Increased rate of lever pressings was evaluated against the frequency of the stimulating current. Increase in rate of lever presses was considered as a measure of reward and reinforcement. About 30-70% increase in self-stimulation was observed following bilateral intra-AcbSh treatment with morphine, NPY or [Leu(31), Pro(34)]-NPY (NPY Y1/Y5 receptors agonist), however, BIBP3226 (selective NPY Y1 receptors antagonist) produced opposite effect. The reward effect of morphine was significantly potentiated by NPY or [Leu(31), Pro(34)]-NPY, but antagonized by BIBP3226. NPY-immunoreactivity in the AcbSh, arcuate nucleus (ARC) and lateral part of bed nucleus of stria terminalis (BNSTl) was significantly more in the operant conditioned rats than in naïve control. However, morphine administration to the conditioned rats resulted in significant decrease in the NPY-immunoreactivity in all these anatomical regions. Since the role of morphine in modulation of mesolimbic-dopaminergic pathway is well established, we suggest that NPY system in AcbSh, ARC and BNSTl, perhaps acting via Y1-receptor system, may be an important component of the mesolimbic-AcbSh reward circuitry triggered by endogenous opioids.