Bicruciate retaining total knee arthroplasty: current state and future promise.

Total knee arthroplasty (TKA) is a well-known surgical procedure performed to address end stage osteoarthritis. The main goal is to relieve pain, recover articular function and return to normal function as soon as possible. Over the years it is frequently performed in the elderly, but lately there is an increased demand in a younger and more active population. Up to 25% of patients feel dissatisfied about their TKA. The anterior cruciate ligament (ACL) is considered the main anteroposterior stabilizer of the knee; nevertheless the ACL is usually sacrificed during conventional TKA. Research shows this might be an unnecessary sacrifice in certain cases. The considerable dissatisfaction rate in mainly high-demanding patients, together with the literature reports on the importance of the ACL function, were the two main reasons for the development of bicruciate retaining (BCR) total knee arthroplasty. BCR TKA may offer superior knee kinematics and proprioception, through anterior cruciate ligament preservation, but requires a higher level of attention to obtain an accurate and precise component orientation to reach proper ligamentous balancing and restore the native knee biomechanics. Many surgeons abandoned its use due to its challenging technique and inconsistent results. Recent new BCR implant designs are promising. This systematic literature review aims to summarize the current state of BCR TKA and what to expect in the future.

Does the application of kinesiotape change scapular kinematics in healthy female handball players?

Elastic taping is widely used in sports medicine for correcting functional alignment and muscle recruitment. However, evidence regarding its influence on scapular dynamic positioning is scarce. This study aimed to investigate the effect of a specific kinesiotaping method on scapular kinematics in female elite handball players without shoulder complaints. 25 athletes (18.0±1.5 years) active in the highest national division were recruited. All subjects received an elastic adhesive tape (K-active tape©) with the purpose to correct scapular position. 3-dimensional scapular motion measurements were performed (Fastrak®) during humeral elevation in the sagittal, frontal and scapular plane. The results showed that taping has a moderate to large effect (Cohen's d>0.7) towards scapular posterior tilting, in all 3 planes of humeral movement and for all angles of elevation (mean posteriorizing effect of 4.23 °, 3.23 ° and 4.33 ° respectively for elevation in the sagittal, frontal and scapular plane, p<0.001). In addition, taping also moderately increased the scapular upward rotation at 30 °, 60 ° and 90 ° of humeral abduction (mean increase of 2.90 °, Cohen's d>0.7). Together these results suggest that kinesiotape application causes positive changes in scapular motion. This could support its use in sports medicine for preventing shoulder problems in overhead athletes.

Changes in microcirculation of the trapezius muscle during a prolonged computer task.

The aim of this study is to investigate if there is a change in oxygen saturation and blood flow in the different parts of the trapezius muscle in office workers with and without trapezius myalgia during a standardized computer task. Twenty right-handed office workers participated; ten were recruited based on pain in the trapezius and ten as matching controls. Subjects performed a combination of typing and mousing tasks for 60 min at a standardized workstation. Muscle tissue oxygenation and blood flow data were collected from the upper trapezius (UT), the middle trapezius (MT) and the lower trapezius (LT), both on the left and right side at seven moments (at baseline and every tenth minute during the 1-h typing task) by use of the oxygen to see device. In all three parts of the trapezius muscle, the oxygen saturation and blood flow decreased significantly over time in a similar pattern (p < 0.001). Oxygenation of the left and right UT was significantly higher compared to the other muscle parts (p < 0.001). Oxygen saturation for the MT was significantly lower in the cases compared to the control group (p = 0.027). Blood flow of the UT on the right side was significantly lower than the blood flow on the left side (p = 0.026). The main finding of this study was that 1 h of combined workstation tasks resulted in decreased oxygen saturation and blood flow in all three parts of the trapezius muscle. Future research should focus on the influence of intervention strategies on these parameters.

Dose-response effect of fish oil substitution in parturition feed on erythrocyte membrane characteristics and sow performance.

The present study aimed to investigate whether n-3 polyunsaturated fatty acids (PUFA) incorporate into erythrocyte membranes of peripartal sows in a dose-responsive manner and whether the altered fatty acid profile affects the cell membrane characteristics. At day 109 of gestation (day 0), 51 sows were divided into five treatment groups. Each group received a diet with a different ratio of fish oil to pork lard for nine consecutive days. Blood samples were taken at day 0 and 10 days later. The fatty acid profile of erythrocytes was determined, as well as the osmotic fragility and oxidative stability of erythrocytes. Thiobarbituric acid reactive substances (TBARS) and ferric reducing ability of plasma (FRAP) were determined in plasma samples. Finally, reproductive and performance parameters of both sows and piglets were recorded until weaning. Supplementation of fish oil during the peripartal period changed the fatty acid profile of erythrocyte membranes in a dose-responsive manner. Although the n-3 PUFA content of erythrocyte membranes increased with increasing amounts of fish oil in the diet, no significant effect on erythrocyte osmotic fragility could be recorded. In contrast, oxidative stability of erythrocytes decreased linearly with increasing amounts of fish oil in the diet. Similarly, both TBARS and FRAP linearly increased with increasing percentages of fish oil in the diet. Neither piglet nor sow performance was influenced by dietary treatments, except for a decrease of both piglet survival and weaning weight with increasing quantities of fish oil supplemented. It is concluded that changes in dietary lipid sources can affect the membrane's fatty acid profile within days, and mainly influences oxidative stability of the cells.

Dietary supplementation with dimethylglycine affects broiler performance and plasma metabolites depending on dose and dietary fatty acid profile.

The effect of dietary supplementation with N,N-dimethylglycine sodium salt (Na-DMG) was evaluated in a feeding trial with 1500 1-day-old broiler chicks (Cobb 500). DMG was supplemented at 0, 0.1, 0.2, 0.5 or 1 g Na-DMG/kg feed to a ration with either animal fat (chicken fat) or vegetal fat (soy oil) as main fat source. In the vegetal fat diets, production value was significantly linearly improved by supplementation with DMG up to 11%. Irrespective of dietary fat source, abdominal fat percentage was significantly linearly reduced up to 24% and meat yield tended to increase linearly with DMG level up to 4%. In the vegetal fat groups, DMG significantly lowered abdominal fat pad by up to 38% and tended to increase meat yield up to 6% at the highest dose. Fasted non-esterified fatty acid level significantly decreased with increasing DMG level up to 36% and thiobarbituric acid reactive species (TBARS) decreased with a statistical trend up to 46% at the highest dose. In vegetal fat diets, addition of DMG resulted in significant lower TBARS level by 56% at the highest dose. Finally, a significant quadratic effect on ascites heart index was present in the vegetal fat diets, with a minimal value at 0.5 g Na-DMG/kg. In conclusion, dietary supplementation with DMG may improve technical and slaughter performance, and may reduce oxidative stress and pulmonary hypertension, but the degree of effects is modulated by fatty acid profile of the diet. Herewith, effects are more pronounced in a diet rich in polyunsaturated fatty acids compared with a diet rich in saturated and monounsaturated fatty acids.

Evaluation of the agreement between Brix refractometry and serum immunoglobulin concentration in neonatal piglets.

Neonatal piglets lack immunoglobulins at birth. Sufficient colostrum intake (CI) and immunoglobulin absorption are essential for an appropriate passive transfer of immunity via the colostrum. Most methods to measure immunoglobulins in serum of piglets are labour-intensive, expensive or imprecise and not designed for on-farm use. The present diagnostic test study evaluated digital Brix refractometry to measure immunoglobulins in serum of neonatal piglets and to suggest thresholds for different serum immunoglobulin concentration. Additionally, agreements between Brix refractometry and optical refractometer (serum total protein, STP) and between Brix refractometry and ELISA (immunoglobulin G, IgG) were also investigated. Forty-five sows and 269 piglets from three different farms were enrolled in the study. Piglets were weighed at birth and 24 h later to calculate the CI. Serum was collected at 24 h after birth and analysed for STP, γ-globulins (electrophoresis), % Brix and IgG. In piglets, median (interquartile range, IQR) CI was 412 (196) g per piglet. Median (IQR) STP, γ-globulin and % Brix concentrations in piglet serum were 60 (11) g/L, 35 (10) g/L and 8 (2) %, respectively. Average (±SD) IgG concentration was 49 ±â€¯23 g/L. Passing-Bablok regression revealed a strong concordance between % Brix and STP (Kendall's tau (Τ): 0.620, P < 0.0001, n = 267) and % Brix and γ-globulin concentration (Kendall's Τ: 0.575, P < 0.0001, n = 267). The agreement between the Brix refractometer and IgG concentration was poor (Kendall's Τ: 0.267, P < 0.0001, n = 269). Receiver operating characteristic curves were performed to evaluate test characteristics of Brix refractometry for three γ-globulin cut-off values, i.e. 10, 20 and 30 g/L. The % Brix cut-off values resulting in the optimal combination of sensitivity and specificity were 5.4 (100 and 98.5%), 7.0 (100 and 89.3%) and 7.9 (90.1 and 80.6%), respectively. In conclusion, digital Brix refractometry is a sufficiently fast and practical method to assess serum γ-globulin concentrations in neonatal piglets on-farm and to evaluate them by considering the thresholds found in this study. Further studies are needed to validate those thresholds regarding piglet's survival in the pre-weaning period.

Electromyographic analysis of knee push up plus variations: what is the influence of the kinetic chain on scapular muscle activity?

OBJECTIVE: First, to look for appropriate closed kinetic chain exercises to restore intramuscular imbalance between upper trapezius (UT) and serratus anterior (SA) in overhead athletes. Second, to determine the influence of using diagonal pattern muscle recruitment during knee push up plus (KPP) exercises on scapular electromyographic activity. DESIGN: Single group repeated-measures design. SETTING: Controlled laboratory study. PARTICIPANTS: Thirty-two physically active individuals in good general health who did not have a history of neck and/or shoulder injury or surgery nor participated in high-level overhead sports or performed upper limb strength training for more than 5 h/week. Interventions Subjects performed the standard KPP and six variations. MAIN OUTCOME MEASUREMENTS: Electromyographic activity of the three trapezius parts and the SA. RESULTS: Four exercises with a low UT/SA can be selected for rehabilitation of intramuscular balance: standard KPP, KPP with homolateral leg extension, KPP with a wobble board and homolateral leg extension and one-handed KPP. The use of a wobble board during KPP exercises and performance on one hand has no influence on SA electromyographic activity. Heterolateral leg extension during KPP stimulates lower trapezius activity, whereas homolateral leg extension stimulates SA activity. CONCLUSIONS: In case of intramuscular scapular imbalance, some exercises are preferable over others because of their low UT/SA ratio. The use of a kinetic chain approach during KPP exercises influences scapular muscle activity.

Dietary N,N-dimethylglycine supplementation improves nutrient digestibility and attenuates pulmonary hypertension syndrome in broilers.

N,N-dimethylglycine (DMG) is an intermediary metabolite in cellular choline and betaine metabolism. The present trial aimed to evaluate the effect of dietary DMG on nutrient digestibility and development of pulmonary hypertension syndrome in broilers. A total of 64 14-day-old broiler hens (Ross-308) were raised until age 40 days under cold environmental temperature conditions (15 °C) and were fed a high energy feed in order to incite pulmonary hypertension. Birds were randomly assigned to two groups of which each group had eight replicate pens of four birds each. Test diets contained 0 or 167 mg Na-DMG (Taminizer(®) D; Taminco N.V., Ghent, Belgium)/kg feed. N,N-dimethylglycine supplementation resulted in a significant improvement in apparent faecal digestibility of crude protein and nitrogen-free extract. Further, fulminant ascites was numerically lowered by DMG and incidence of pulmonary hypertension decreased significantly from 44.8% in the control group to 14.6% in the DMG group. Finally, fasted plasma level of non-esterified fatty acids (NEFA) was twofold in the control group in relation to the DMG group. In conclusion, these data demonstrate beneficial effects of DMG on digestibility of non-fat fractions, on fat metabolism and on progression towards broiler ascites syndrome.

Accumbal noradrenaline that contributes to the alpha-adrenoceptor-mediated release of dopamine from reserpine-sensitive storage vesicles in the nucleus accumbens is derived from alpha-methyl-para-tyrosine-sensitive pools.

Alpha-adrenoceptors in the nucleus accumbens are known to inhibit accumbal dopamine release from reserpine-sensitive pools. The aim of this study was to test our previously reported hypothesis that accumbal noradrenaline that controls the dopamine release from these storage vesicles is derived from alpha-methyl-para-tyrosine-sensitive pools. The sensitivity of accumbal alpha-adrenoceptors to noradrenergic agents depends on the amount of noradrenaline that is available in the synapse. In case the synaptic noradrenaline levels decrease, the conformation of alpha-adrenoceptors changes into a state that makes these receptors more sensitive to its agonists. The effects of alpha-methyl-para-tyrosine, respectively reserpine, on the alpha-adrenoceptor-agonist-induced changes of accumbal dopamine release were investigated. Alpha-methyl-para-tyrosine, but not reserpine, made accumbal postsynaptic alpha-adrenoceptors more sensitive to phenylephrine. These results indicate that noradrenaline that inhibits the release of dopamine from reserpine-sensitive storage vesicles, via stimulation of accumbal postsynaptic alpha-adrenoceptors, is derived from alpha-methyl-para-tyrosine-sensitive pools. The clinical impact of these data is discussed.

Effect of proprioceptive neuromuscular facilitation stretching on the plantar flexor muscle-tendon tissue properties.

Proprioceptive neuromuscular facilitation (PNF) stretching programs have been shown to be the most effective stretching technique to increase the range of motion (ROM). The objective of this study was to examine the mechanism of effect of PNF stretching on changes in the ROM. Sixty-two healthy subjects were randomized into two groups: a PNF stretching group and a control group. The PNF group performed a 6-week stretching program for the calf muscles. Before and after this period, all subjects were evaluated for dorsiflexion ROM, passive resistive torque (PRT) of the plantar flexors and stiffness of the Achilles tendon. The results of the study revealed that the dorsiflexion ROM was significantly increased in the PNF group (DeltaROMext: 5.97+/-0.671 degrees ; DeltaROMflex: 5.697+/-0.788 degrees ). The PRT of the plantar flexors and the stiffness of the Achilles tendon did not change significantly after 6 weeks of PNF stretching. These findings provide evidence that PNF stretching results in an increased ankle dorsiflexion. However, this increase in ROM could not be explained by a decrease of the PRT or by a change in stiffness of the Achilles tendon, and therefore can be explained by an increase in stretch tolerance.

A prospective study on gait-related intrinsic risk factors for lower leg overuse injuries.

OBJECTIVE: To determine prospectively gait-related risk factors for lower leg overuse injury (LLOI). DESIGN: A prospective cohort study. SETTING: Male and female recruits from a start-to-run (STR) programme during a 10-week training period. PARTICIPANTS: 131 healthy subjects (20 men and 111 women), without a history of any lower leg complaint, participated in the study. INTERVENTIONS: Before the start of the 10-week STR programme, plantar force measurements during running were performed. During STR, lower leg injuries were diagnosed and registered by a sports physician. MAIN OUTCOME MEASURES: Plantar force measurements during running were performed using a footscan pressure plate. RESULTS: During the STR, 27 subjects (five men and 22 women) developed a LLOI. Logistic regression analysis revealed that subjects who developed a LLOI had a significantly more laterally directed force distribution at first metatarsal contact and forefoot flat, a more laterally directed force displacement in the forefoot contact phase, foot flat phase and at heel-off. These subjects also had a delayed change of the centre of force (COF) at forefoot flat, a higher force and loading underneath the lateral border of the foot, and a significantly higher directed force displacement of the COF at forefoot flat. CONCLUSIONS: These findings suggest that a less pronated heel strike and a more laterally directed roll-off can be considered as risk factors for LLOI. Clinically, the results of this study can be considered important in identifying individuals at risk of LLOI.

A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders.

Human studies have shown that a reduction of 5-HT transporter (SERT) increases the vulnerability for anxiety and depression. Moreover, women are more vulnerable to develop depression and anxiety disorders than men. For that reason we hypothesized that homozygous 5-HT transporter knockout rat (SERT(-/-)) models, especially female, are valuable and reliable animal models for humans with an increased vulnerability for anxiety- and depression-related disorders. As rats are extensively used in neuroscience research, we used the unique 5-HT transporter knockout rat, that was recently generated using N-ethyl-N-nitrosurea (ENU) -driven mutagenesis, to test this hypothesis. Behavioral testing revealed that male and female SERT(-/-) rats spent less time in the center of the open field and spent less time on the open arm of the elevated plus maze compared with wild-type 5-HT transporter knockout rats (SERT(+/+)). In the novelty suppressed feeding test, only male SERT(-/-) rats showed a higher latency before starting to eat in a bright novel arena compared with SERT(+/+) controls. Both male and female SERT(-/-) rats showed a higher escape latency from their home cage than SERT(+/+) littermates. Moreover, SERT(-/-) rats were less mobile in the forced swim test, and sucrose consumption was reduced in SERT(-/-) rats relative to SERT(+/+) rats. Both effects were sex-independent. Neurochemically, basal extracellular 5-HT levels were elevated to a similar extent in male and female SERT(-/-) rats, which was not influenced by the selective 5-HT reuptake inhibitor citalopram. 5-HT immunostaining revealed no difference between SERT(+/+) and SERT(-/-) rats in the dorsal raphe nuclei, in both males and females. These findings demonstrate that SERT(-/-) rats show anxiety and depression-related behavior, independent of sex. Genetic inactivation of the SERT has apparently such a great impact on behavior, that hardly any differences are found between male and female rats. This knockout rat model may provide a valuable model to study anxiety- and depression-related disorders in male and female rats.

Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats.

RATIONALE: Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats. OBJECTIVES: As individual differences exist in central serotonin neurotransmission, the impact of ATD may vary accordingly. In this experiment, we investigated the hypothesis that male serotonin transporter knockout (SERT(-/-)), rats marked by a lower SERT function, are more vulnerable to the effects of ATD in an object recognition task than male wildtype (SERT(+/+)) and heterozygous (SERT(+/-)) rats. MATERIALS AND METHODS: Twelve male SERT(+/+), SERT(+/-), and SERT(-/-) rats were treated with standard dose and low-dose ATD using a gelatine-based protein-carbohydrate mixture lacking tryptophan. In the control treatment, L: -tryptophan was added to the mixture. Four hours after treatment, the rats were subjected to the object recognition task. In addition, the effects of ATD on plasma amino acid concentrations were measured, and concentrations of 5-HT and 5-HIAA were measured in the frontal cortex and hippocampus of these rats. RESULTS: Plasma TRP levels and central 5-HT and 5-HIAA levels were decreased in all genotypes after ATD, but effects were stronger in SERT(-/-) rats. The standard dose of ATD impaired object recognition in all genotypes. SERT(-/-) and SERT(+/-) rats were more vulnerable to low dose of ATD in the object recognition task compared to SERT(+/+) rats. CONCLUSIONS: These results indicate a greater sensitivity to ATD in SERT(-/-) and SERT(+/-) rats, which may be related to stronger central depletion effects in these rats.

Screening the athlete's shoulder for impingement symptoms: a clinical reasoning algorithm for early detection of shoulder pathology.

Chronic shoulder pain and dysfunction are common complaints among overhead athletes seeking care from physical medicine and rehabilitation. Impingement is a frequently described pathological condition in the overhead athlete. Impingement symptoms may be the result of rotator cuff pathology, shoulder instability, scapular dyskinesis or muscle dysfunction, biceps pathology, SLAP lesions and chronic stiffness of the posterior capsule. At present, numerous different shoulder tests have been described in literature and discussed with respect to their individual diagnostic accuracy. However, in view of the number of shoulder tests, it is often a challenge for the clinician to select the appropriate tests for diagnosing the underlying pathology. The purpose of this paper is to present and discuss a clinical algorithm which may be used in the early detection of the underlying causes of impingement symptoms. In this algorithm, a specific chronology and selection of diagnostic tests may offer the clinician a guideline in his physical examination of the athlete with shoulder pain.

Internal impingement in the tennis player: rehabilitation guidelines.

Internal impingement is a commonly described cause of shoulder pain in the overhead athlete, particularly in tennis players. Three shoulder dysfunctions, often correlated with internal impingement symptoms, require attention in the rehabilitation strategy of internal impingement in the tennis player: (1) acquired glenohumeral anterior instability, (2) loss of internal rotation range of motion, and (3) lack of retraction strength. Based on recent literature, the following guidelines are proposed in the rehabilitation of the tennis player with internal impingement symptoms: (1) shoulder rehabilitation should be integrated into kinetic chain training, not only in the advanced phases of the athlete's rehabilitation, but from the initial phases; (2) both angular and translational mobilisations can be used in the treatment of acquired loss of glenohumeral internal rotation range of motion to stretch the posterior structures of the glenohumeral joint; and 3) in the rehabilitation of scapular dyskinesis, the therapist should focus on restoration of intramuscular trapezius muscle balance in the scapular exercises, with special attention to strength training of the retractors.

Characterization of the serotonin transporter knockout rat: a selective change in the functioning of the serotonergic system.

Serotonergic signaling is involved in many neurobiological processes and disturbed 5-HT homeostasis is implicated in a variety of psychiatric and addictive disorders. Here, we describe the functional characterization of the serotonin transporter (SERT) knockout rat model, that is generated by N-ethyl-N-nitrosurea (ENU)-driven target-selected mutagenesis. Biochemical characterization revealed that SERT mRNA and functional protein are completely absent in homozygous knockout (SERT-/-) rats, and that there is a gene dose-dependent reduction in the expression and function of the SERT in heterozygous knockout rats. As a result, 5-HT homeostasis was found to be severely affected in SERT-/- rats: 5-HT tissue levels and depolarization-induced 5-HT release were significantly reduced, and basal extracellular 5-HT levels in the hippocampus were ninefold increased. Interestingly, we found no compensatory changes in in vitro activity of tryptophan hydroxylase and monoamine oxidase, the primary enzymes involved in 5-HT synthesis and degradation, respectively. Similarly, no major adaptations in non-serotonergic systems were found, as determined by dopamine and noradrenaline transporter binding, monoamine tissue levels, and depolarization-induced release of dopamine, noradrenaline, glutamate and GABA. In conclusion, neurochemical changes in the SERT knockout rat are primarily limited to the serotonergic system, making this novel rat model potentially very useful for studying the behavioral and neurobiological consequences of disturbed 5-HT homeostasis.

Role of alpha adrenoceptors in the nucleus accumbens in the control of accumbal noradrenaline efflux: a microdialysis study with freely moving rats.

Microdialysis technique was used to study the effects of the locally applied alpha adrenoceptor agonist phenylephrine and antagonist phentolamine on the basal noradrenaline efflux as well as on the noradrenaline uptake inhibitor desipramine-elicited noradrenaline efflux in the nucleus accumbens (NAc) of freely moving rats. Tetrodotoxin reduced basal noradrenaline efflux by 72%, whereas desipramine increased it by 204%. Phenylephrine reduced the basal noradrenaline efflux by 32% and phentolamine blocked this effect. Phentolamine elevated the basal noradrenaline efflux by 150% and phenylephrine counteracted this effect. The desipramine-elicited noradrenaline efflux was not affected by phenylephrine, but enhanced by phentolamine. Desipramine counteracted the effects of phenylephrine and potentiated those of phentolamine. These results indicate that the accumbal noradrenaline efflux is under inhibitory control of alpha adrenoceptors that are suggested to be presynaptically located on adrenergic nerve terminals in the NAc. Furthermore, this study suggests that the conformational state of alpha adrenoceptors varies across the available amount of noradrenaline. The clinical impact of these data is discussed.

Interactions among mu- and delta-opioid receptors, especially putative delta1- and delta2-opioid receptors, promote dopamine release in the nucleus accumbens.

The effect of interactions among mu- and delta-opioid receptors, especially the putative delta(1)- and delta(2)-opioid receptors, in the nucleus accumbens on accumbal dopamine release was investigated in awake rats by in vivo brain microdialysis. In agreement with previous studies, perfusion of the nucleus accumbens with the mu-, delta(1)- and delta(2)-opioid receptor agonists [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), [D-Pen(2,5)]-enkephalin (DPDPE) and [D-Ser(2)]Leu-enkephalin-Thr(6), respectively, significantly enhanced the extracellular amount of accumbal dopamine in a dose-related manner (5.0 nmol and 50.0 nmol). However, the highest concentration tested (50.0 nmol) of DAMGO induced a biphasic effect, i.e. a rapid onset increase lasting for 75 min followed by a slower onset gradual and prolonged increase. The mu-opioid receptor antagonist D-Phe-Cys-Tyr-d-Trp-Orn-Thr-Phe-Thr-NH(2) (0.15 nmol) primarily reduced the DAMGO-induced second component. The delta(1)-opioid receptor antagonist (E)-7-benzylidenenaltrexone (0.15 nmol) significantly reduced the first component and abolished the second component induced by DAMGO, while the delta(2)-opioid receptor antagonist naltriben (1.5 nmol) significantly reduced only the first component. The DPDPE (50.0 nmol)-induced dopamine increase was almost completely abolished by (E)-7-benzylidenenaltrexone, but only partially reduced by D-Phe-Cys-Tyr-d-Trp-Orn-Thr-Phe-Thr-NH(2) and naltriben. The [D-Ser(2)]Leu-enkephalin-Thr(6) (50.0 nmol)-induced dopamine increase was almost completely abolished by naltriben, but not at all by D-Phe-Cys-Tyr-d-Trp-Orn-Thr-Phe-Thr-NH(2) and (E)-7-benzylidenenaltrexone. The non-selective opioid receptor antagonist naloxone (0.75 and 1.5 nmol) dose-dependently reduced the effects of DAMGO, DPDPE and [D-Ser(2)]Leu-enkephalin-Thr(6) but only to about 10-25% of the control values. Moreover, perfusion with the sodium channel blocker tetrodotoxin (0.1 nmol) reduced the DAMGO-induced dopamine increase by 75%, while it almost completely abolished the increase induced by DPDPE or [D-Ser(2)]Leu-enkephalin-Thr(6). The results show that stimulation of mu-opioid receptors or, to a lesser degree, delta(1)-opioid receptors results in a large naloxone-sensitive increase and a small naloxone-insensitive increase of extracellular dopamine. It is suggested that the naloxone-insensitive component is also tetrodotoxin-insensitive. Furthermore, it is hypothesized that stimulation of mu-opioid receptors activates delta(1)-receptors, which in turn activate delta(2)-opioid receptors, thereby giving rise to a rapid onset increase of extracellular dopamine. In addition, it is hypothesized that stimulation of another group of mu-opioid receptors activates a second group of delta(1)-opioid receptors that is not coupled to delta(2)-opioid receptors and mediates a slow onset increase of extracellular dopamine. Finally, it is suggested that stimulation of delta(1)- or delta(2)-opioid receptors inhibits mu-opioid receptors involved in the slow onset increase in extracellular dopamine, whereas stimulation of delta(1)-, but not delta(2)-, opioid receptors is suggested to activate mu-opioid receptors involved in the rapid increase in extracellular dopamine.

Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of dexamphetamine.

Systemic administration of high doses of dexamphetamine induces a dopamine efflux that has its intracellular origin in both the vesicular, reserpine-sensitive dopamine pool and the cytosolic, alpha-methyl-para-tyrosine-sensitive, newly synthesized dopamine pool. It remains unknown whether locally administered dexamphetamine produces similar effects. Using a brain microdialysis technique that is combined with a microinjection needle, the contribution of the vesicular and cytosolic pools to the dopamine efflux induced by striatal injection of dexamphetamine was analyzed in rats. The transient striatal dopamine efflux induced by intrastriatal injection of dexamphetamine (1.0 microg/0.5 microl) was significantly reduced by systemic administration of reserpine (5mg/kg i.p., given 24 h earlier) or alpha-methyl-para-tyrosine (250 mg/kg i.p., given 2 h earlier). The effects of dexamphetamine on the striatal dopamine were nearly nullified by combined treatment with reserpine and alpha-methyl-para-tyrosine. The sum of the amounts of extracellular dopamine that was sensitive to either reserpine or alpha-methyl-para-tyrosine, was far greater than 100%, namely 146.1% of the basal dopamine level and 144.0% of the dexamphetamine-induced dopamine level. The present study indicates that both the vesicular dopamine pool and the cytosolic dopamine pool contribute to the transient increase of striatal dopamine efflux induced by intrastriatal injection of dexamphetamine. This study also suggests that striatally applied dexamphetamine can promote the redistribution of rat striatal dopamine from vesicles to the cytosol in vivo.

Effects of chronic paroxetine pretreatment on (+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin induced c-fos expression following sexual behavior.

Chronic treatment with the selective serotonin reuptake inhibitor paroxetine impairs the functioning of 5-HT(1A) receptors involved in ejaculation. This could underlie the development of delayed ejaculation often reported by men treated with paroxetine. The neurobiological substrate linking the effects of selective serotonin reuptake inhibitor-treatment and 5-HT(1A) receptor activation with ejaculation was investigated. Male Wistar rats that were pretreated with paroxetine (20 mg/kg/day p.o.) or vehicle for 22 days and had received an additional injection with the 5-HT(1A) receptor agonist 8-OH-DPAT ((+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin; 0.4 mg/kg s.c.) or saline on day 22, 30 min prior to a sexual behavior test, were perfused 1 h after the sexual behavior test. Brains were processed for Fos-, and oxytocin immunohistochemistry. The drug treatments markedly changed both sexual behavior and the pattern and number of Fos-immunoreactive cells in the brain. Chronic pretreatment with paroxetine caused delayed ejaculation. Acute injection with 8-OH-DPAT facilitated ejaculation in vehicle-pretreated rats, notably evident in a strongly reduced intromission frequency, whereas 8-OH-DPAT had no effects in paroxetine-pretreated rats. Chronic treatment with paroxetine reduced Fos-immunoreactivity in the locus coeruleus, and prevented the increase in Fos-immunoreactive neurons induced by 8-OH-DPAT in the oxytocinergic magnocellular part of the paraventricular nucleus as well as in the locus coeruleus. Since oxytocin and noradrenalin facilitate ejaculation, the alterations in Fos-IR in these areas could connect selective serotonin reuptake inhibitor treatment and 5-HT(1A) receptor activation to ejaculation. Chronic paroxetine treatment and 8-OH-DPAT changed c-fos expression in a number of other brain areas, indicating that Fos-immunohistochemistry is a useful tool to find locations where selective serotonin reuptake inhibitors and 8-OH-DPAT exert their effects.