The effect of estrogen on brown adipose tissue activity in male rats.

OBJECTIVE: Centrally administered estrogen can increase sympathetic nerve activity to brown adipose tissue, resulting in thermogenesis. The central thermogenic effects of estrogen have not been investigated in males. Therefore, this study sought to investigate the effects of peripherally and centrally administered estrogen on thermogenesis, heart rate and mean arterial pressure in male rats. Thermogenesis was assessed by monitoring brown adipose tissue temperature. RESULTS: Peripherally administered estrogen elicited no significant effect on brown adipose tissue temperature, heart rate or mean arterial pressure. Centrally administered estrogen elicited a coincident increase in both brown adipose tissue and core temperature. Centrally administered estrogen also resulted in a decrease in mean arterial pressure but had no effect on heart rate. With the present data it is not possible to elucidate whether changes in temperature were the result of thermogenic or thermoregulatory mechanisms.

Stimulatory, but not anxiogenic, doses of caffeine act centrally to activate interscapular brown adipose tissue thermogenesis in anesthetized male rats.

The role of central orexin in the sympathetic control of interscapular brown adipose tissue (iBAT) thermogenesis has been established in rodents. Stimulatory doses of caffeine activate orexin positive neurons in the lateral hypothalamus, a region of the brain implicated in stimulating BAT thermogenesis. This study tests the hypothesis that central administration of caffeine is sufficient to activate BAT. Low doses of caffeine administered either systemically (intravenous [IV]; 10 mg/kg) and centrally (intracerebroventricular [ICV]; 5-10 µg) increases BAT thermogenesis, in anaesthetised (1.5 g/kg urethane, IV) free breathing male rats. Cardiovascular function was monitored via an indwelling intra-arterial cannula and exhibited no response to the caffeine. Core temperature did not significantly differ after administration of caffeine via either route of administration. Caffeine administered both IV and ICV increased neuronal activity, as measured by c-Fos-immunoreactivity within subregions of the hypothalamic area, previously implicated in regulating BAT thermogenesis. Significantly, there appears to be no neural anxiety response to the low dose of caffeine as indicated by no change in activity in the basolateral amygdala. Having measured the physiological correlate of thermogenesis (heat production) we have not measured indirect molecular correlates of BAT activation. Nevertheless, our results demonstrate that caffeine, at stimulatory doses, acting via the central nervous system can increase thermogenesis, without adverse cardio-dynamic impact.

Perineal resuturing versus expectant management following vaginal delivery complicated by a dehisced wound (PREVIEW): a pilot and feasibility randomised controlled trial.

OBJECTIVE: To establish the feasibility of conducting a definitive randomised controlled trial (RCT) comparing the effectiveness of resuturing versus expectant management for dehisced perineal wounds. DESIGN: A multicentre pilot and feasibility RCT. SETTING: Ten UK maternity units from July 2011 to July 2013. POPULATION: Eligible women with a dehisced perineal wound within 2 weeks of childbirth. METHODS: The interventions were resuturing or expectancy. Randomisation was via web or telephone, stratified by participating centre. Blinding was not possible due to the nature of the interventions. Analysis was by intention-to-treat. OUTCOME: The primary outcome measure was wound healing at 6-8 weeks. RESULTS: The study revealed a number of feasibility issues, particularly strong patient and clinician preference for treatment options at recruiting centres and the timing of the primary outcome measure. Thirty-four women were randomised (17 in each arm). Data from 33 women were analysed on an intention-to-treat analysis to obtain preliminary estimates of effect size. There was a difference in wound healing at 2 weeks favouring resuturing (OR 20.00, 95% CI 2.04 to 196.37, p=0.004). However, by 6-8 weeks all but one wound in both groups had healed. CONCLUSIONS: PREVIEW revealed a number of feasibility issues, which impacted on recruitment rate. These will have to be taken into account in the design of any future definitive study. In this feasibility study, resuturing was associated with quicker wound healing and women reported higher satisfaction rates with the outcome at 3 months. TRIAL REGISTRATION NUMBER: ISRCTN05754020.

Perineal resuturing versus expectant management following vaginal delivery complicated by a dehisced wound (PREVIEW): a nested qualitative study.

OBJECTIVE: To explore women's lived experiences of a dehisced perineal wound following childbirth and how they felt participating in a pilot and feasibility randomised controlled trial (RCT). DESIGN: A nested qualitative study using semistructured interviews, underpinned by descriptive phenomenology. PARTICIPANTS AND SETTING: A purposive sample of six women at 6-9 months postnatal who participated in the RCT were interviewed in their own homes. RESULTS: Following Giorgi's analytical framework the verbatim transcripts were analysed for key themes. Women's lived experiences revealed 4 emerging themes: (1) Physical impact, with sub-themes focusing upon avoiding infection, perineal pain and the impact of the wound dehiscence upon daily activities; (2) Psychosocial impact, with sub-themes of denial, sense of failure or self-blame, fear, isolation and altered body image; (3) Sexual impact; and (4) Satisfaction with wound healing. A fifth theme 'participating in the RCT' was 'a priori' with sub-themes centred upon understanding the randomisation process, completing the trial questionnaires, attending for hospital appointments and acceptability of the treatment options. CONCLUSIONS: To the best of our knowledge, this is the first qualitative study to grant women the opportunity to voice their personal experiences of a dehisced perineal wound and their views on the management offered. The powerful testimonies presented disclose the extent of morbidity experienced while also revealing a strong preference for a treatment option. TRIAL REGISTRATION NUMBER: ISRCTN05754020; results.

Evaluation of accuracy of mediolateral episiotomy incisions using a training model.

BACKGROUND: Episiotomy is one of the most commonly performed surgical procedures worldwide. In the UK the use of episiotomy is selective, rather than routine, and a right mediolateral episiotomy (RMLE) is considered standard practice. According to The National Institute of Health and Care Excellence (NICE, 2007) guideline for intrapartum care such an episiotomy should be cut at an angle between 45° and 60° to the vertical axis. Recent evidence suggests that the angle of incision of mediolateral episiotomy (MLE) is associated with risk of obstetric anal sphincter injury (OASIS). OBJECTIVE: to assess the accuracy of individual practitioner's techniques when performing a RMLE. DESIGN: an audit of practice against nationally set standards. SETTING: at a national midwifery conference and prior to three multiprofessional perineal repair training workshops in the West Midlands region of the UK. PARTICIPANTS: 144 midwives and 53 obstetric trainees. MEASUREMENTS: practitioners were asked to perform a RMLE incision on a bespoke training model, which is designed to give a realistic representation of a stretched perineum at crowning of the baby's head. Four parameters were measured: (1) distance of the starting point from the midline; (2) angle subtended to the perpendicular; (3) length and (4) shape of the incision (curved, straight or J-shaped). FINDINGS: of the 197 incisions performed only 12.7% (14.6%, n=21/144 of midwives and 7.5%, n=4/53 of obstetricians) complied with the defined technique of a RMLE for correctness of angle and placement. A 2-sided Fisher's exact test showed no significant difference between previous attendance at perineal management training and incision accuracy.

Evaluating contemporary pollen dispersal in two common grassland species Ranunculus bulbosus L. (Ranunculaceae) and Trifolium montanum L. (Fabaceae) using an experimental approach.

Pollen flow is a key biological process that connects plant populations, preventing genetic impoverishment and inbreeding. Pollen-mediated long-distance dispersal (LDD) events are especially important for plant species in increasingly fragmented landscapes. Patterns of pollen dispersal were directly estimated and dispersal kernels modelled in an experimental population of Ranunculus bulbosus and Trifolium montanum to determine the potential for LDD. Eight and 11 microsatellite markers were used for R. bulbosus and T. montanum, respectively, to run a likelihood-based paternity analysis on randomly chosen offspring (Ntotal = 180 per species) from five maternal plants. High rates of selfing were found in R. bulbosus (average 45.7%), while no selfing was observed in T. montanum. The majority (60%) of mating events occurred at very short distances: the median of the observed dispersal distances was 0.8 m in both species, and the average distances were 15.9 and 10.3 m in R. bulbosus and T. montanum, respectively. Modelling the pollen dispersal kernel with four different distribution functions (exponential-power, geometric, 2Dt and Weibull) indicated that the best fit for both species was given by a Weibull function. Yet, the tail of the T. montanum pollen dispersal kernel was thinner than in R. bulbosus, suggesting that the probability for LDD is higher in the latter species. Even though the majority of pollen dispersal occurred across short distances, the detection of several mating events up to 362 m (R. bulbosus) and 324 m (T. montanum) suggests that pollen flow may be sufficient to ensure population connectivity in these herb species across fragmented grasslands in Swiss agricultural landscapes.

Does long-distance pollen dispersal preclude inbreeding in tropical trees? Fragmentation genetics of Dysoxylum malabaricum in an agro-forest landscape.

Tropical trees often display long-distance pollen dispersal, even in highly fragmented landscapes. Understanding how patterns of spatial isolation influence pollen dispersal and interact with background patterns of fine-scale spatial genetic structure (FSGS) is critical for evaluating the genetic consequences of habitat fragmentation. In the endangered tropical timber tree Dysoxylum malabaricum (Meliaceae), we apply eleven microsatellite markers with paternity and parentage analysis to directly estimate historic gene flow and contemporary pollen dispersal across a large area (216 km(2)) in a highly fragmented agro-forest landscape. A comparison of genetic diversity and genetic structure in adult and juvenile life stages indicates an increase in differentiation and FSGS over time. Paternity analysis and parentage analysis demonstrate high genetic connectivity across the landscape by pollen dispersal. A comparison between mother trees in forest patches with low and high densities of adult trees shows that the frequency of short-distance mating increases, as does average kinship among mates in low-density stands. This indicates that there are potentially negative genetic consequences of low population density associated with forest fragmentation. Single isolated trees, in contrast, frequently receive heterogeneous pollen from distances exceeding 5 km. We discuss the processes leading to the observed patterns of pollen dispersal and the implications of this for conservation management of D. malabaricum and tropical trees more generally.

Forest fragmentation genetics in a formerly widespread island endemic tree: Vateriopsis seychellarum (Dipterocarpaceae).

Habitat fragmentation and changed land use have seriously reduced population size in many tropical forest tree species. Formerly widespread species with limited gene flow may be particularly vulnerable to the negative genetic effects of forest fragmentation and small population size. Vateriopsis seychellarum (Dipterocarpaceae) is a formerly widespread canopy tree of the Seychelles, but is now reduced to 132 adult individuals distributed in eleven sites. Using ten microsatellite loci, a genetic inventory of all adult trees and a sample of 317 progeny, we demonstrate that despite its restricted range, overall genetic diversity was relatively high (H(E) : 0.56). The juvenile cohort, however, had significantly lower allelic richness (adults R(S) : 3.91; juveniles R(S) : 2.83) and observed heterozygosity than adult trees (adults H(O) : 0.62; juveniles H(O) : 0.48). Rare alleles were fewer and kinship between individuals was stronger in juveniles. Significant fine-scale spatial genetic structure was observed in remnant adults, and parentage analysis indicated that more than 90% of sampled progeny disperse <25 m and pollen dispersed <50 m. The molecular data confirmed that two populations were derived entirely from self-fertilized offspring from a single surviving mother tree. These populations produce viable offspring. Despite this extreme genetic bottleneck, self-compatibility may provide V. seychellarum with some resistance to the genetic consequences of habitat fragmentation, at least in the short term. We discuss our findings in the context of other rare and threatened dipterocarp species which are vulnerable to miss-management of genetic resources and population fragmentation.

Back from the brink: potential for genetic rescue in a critically endangered tree.

Rare plant species are vulnerable to genetic erosion and inbreeding associated with small population size and isolation due to increasing habitat fragmentation. The degree to which these problems undermine population viability remains debated. We explore genetic and reproductive processes in the critically endangered long-lived tropical tree Medusagyne oppositifolia, an endemic to the Seychelles with a naturally patchy distribution. This species is failing to recruit in three of its four populations. We evaluate whether recruitment failure is linked to genetic problems associated with fragmentation, and if genetic rescue can mitigate such problems. Medusagyne oppositifolia comprises 90 extant trees in four populations, with only the largest (78 trees) having successful recruitment. Using 10 microsatellite loci, we demonstrated that genetic diversity is high (H(E) : 0.48-0.63; H(O) : 0.56-0.78) in three populations, with only the smallest population having relatively low diversity (H(E) : 0.26 and H(O) : 0.30). All populations have unique alleles, high genetic differentiation, and significant within population structure. Pollen and seed dispersal distances were mostly less than 100 m. Individuals in small populations were more related than individuals in the large population, thus inbreeding might explain recruitment failure in small populations. Indeed, inter-population pollination crosses from the large donor population to a small recipient population resulted in higher reproductive success relative to within-population crosses. Our study highlights the importance of maintaining gene flow between populations even in species that have naturally patchy distributions. We demonstrate the potential for genetic and ecological rescue to support conservation of plant species with limited gene flow.

Continuous versus interrupted sutures for repair of episiotomy or second degree tears.

BACKGROUND: Millions of women worldwide undergo perineal suturing after childbirth and the type of repair may have an impact on pain and healing. For more than 70 years, researchers have been suggesting that continuous non-locking suture techniques for repair of the vagina, perineal muscles and skin are associated with less perineal pain than traditional interrupted methods. OBJECTIVES: To assess the effects of continuous versus interrupted absorbable sutures for repair of episiotomy and second degree perineal tears following childbirth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 2007). SELECTION CRITERIA: Randomised trials comparing continuous versus interrupted sutures for repair of episiotomy and second-degree tears after vaginal delivery. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trial quality. Two of the three authors independently extracted data and a third author checked them. We contacted study authors for additional information. MAIN RESULTS: Seven studies, involving 3822 women at point of entry, from four countries, have been included. The trials were heterogeneous in respect of operator skill and training. Meta-analysis showed that continuous suture techniques compared with interrupted sutures for perineal closure (all layers or perineal skin only) are associated with less pain for up to 10 days postpartum (relative risk (RR) 0.70, 95% confidence interval 0.64 to 0.76). Subgroup analysis showed that there is a greater reduction in pain when continuous suturing techniques are used for all layers (RR 0.65, 95% CI 0.60 to 0.71). There was an overall reduction in analgesia use associated with the continuous subcutaneous technique versus interrupted stitches for repair of perineal skin (RR 0.70, 95% CI 0.58 to 0.84). Subgroup analysis showed some evidence of reduction in dyspareunia experienced by participants in the groups that had continuous suturing for all layers (RR 0.83, 95% CI 0.70 to 0.98). There was also a reduction in suture removal in the continuous suturing groups versus interrupted (RR 0.54, 95% CI 0.45 to 0.65), but no significant differences were seen in the need for re-suturing of wounds or long-term pain. AUTHORS' CONCLUSIONS: The continuous suturing techniques for perineal closure, compared to interrupted methods, are associated with less short-term pain. Moreover, if the continuous technique is used for all layers (vagina, perineal muscles and skin) compared to perineal skin only, the reduction in pain is even greater.

Identifying the early genetic consequences of habitat degradation in a highly threatened tropical conifer, Araucaria nemorosa Laubenfels.

The early genetic effects of habitat degradation were investigated in the critically endangered conifer Araucaria nemorosa. This species occurs in New Caledonia, a global biodiversity hotspot where the world's greatest concentration of endemic conifer species coincides with an extremely high level of habitat destruction due to fire and mining. Using seven microsatellite loci, estimates were made of genetic marker variation, inbreeding coefficients and population differentiation of adult and seedling cohorts of A. nemorosa. These were contrasted with equivalent estimates, made over similar spatial scales and with the same marker loci, in the locally common and more widespread sister species Araucaria columnaris. There were no significant differences in population genetic parameters between adult populations of the two species, despite their different abundances. However, in A. nemorosa, the juvenile cohort showed a loss of rare alleles and elevated levels of inbreeding when compared to the adult cohort. These genetic differences between the cohorts were not observed in the locally common A. columnaris. This suggests that recent environmental degradation is influencing the genetic structure of A. nemorosa populations. Although this is not detectable among predisturbance adult populations, an early warning of these impacts is evident in more recently established seedling cohorts. The conservation implications of these results are discussed.

Methods of repair for obstetric anal sphincter injury.

BACKGROUND: Anal sphincter injury during childbirth - obstetric anal sphincter injuries (OASIS) - is associated with significant maternal morbidity including perineal pain, dyspareunia and anal incontinence. Anal incontinence affects women psychologically and physically. Many do not seek medical attention because of embarrassment. The two recognised methods for the repair of damaged external anal sphincter (EAS): are end-to-end (approximation) repair and overlap repair. OBJECTIVES: To compare the effectiveness of overlap repair versus end-to-end repair following OASIS in reducing subsequent anal incontinence, perineal pain, dyspareunia and improving quality of life. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 January 2006), MEDLINE (January 1966 to 31 January 2006), EMBASE (January 1974 to 31 January 2006), SciSearch (January 1974 to 31 January 2006) and conference proceedings of obstetrics and gynaecology, surgery and coloproctology. SELECTION CRITERIA: Randomised controlled trials comparing different techniques of immediate primary repair of EAS following OASIS. DATA COLLECTION AND ANALYSIS: Trial quality was assessed independently by all authors. MAIN RESULTS: Three eligible trials, of grade A quality, involving 279 women, were included. There was considerable heterogeneity in the outcome measures, time points and reported results. Meta-analyses showed that there was no statistically significant difference in perineal pain (relative risk (RR) 0.08, 95% confidence interval (CI) 0.00 to 1.45, one trial, 52 women), dyspareunia (RR 0.62, 95% CI 0.11 to 3.39, one trial, 52 women), flatus incontinence (RR 0.93, 95% CI 0.26 to 3.31, one trial, 52 women) and faecal incontinence (RR 0.07, 95% CI 0.00 to 1.21, one trial, 52 women) between the two repair techniques at 12 months but showed a statistically significantly lower incidence in faecal urgency (RR 0.12, 95% CI 0.02 to 0.86, one trial, 52 women) and lower anal incontinence score (weighted mean difference -1.70, 95% CI -3.03 to -0.37) in the overlap group. Overlap technique was also associated with a statistically significant lower risk of deterioration of anal incontinence symptoms over 12 months (RR 0.26, 95% CI 0.09 to 0.79, one trial, 41 women). There was no significant difference in quality of life. AUTHORS' CONCLUSIONS: The limited data available show that compared to immediate primary end-to-end repair of OASIS, early primary overlap repair appears to be associated with lower risks for faecal urgency and anal incontinence symptoms. As the experience of the surgeon is not addressed in the three studies reviewed, it woudl be inappropriate to recommend one type of repair in favour of another.

Geographic patterning of variation in segment number in geophilomorph centipedes: clines and speciation.

Since their origin as a metameric group, arthropods have diversified considerably in their number of segments. Present-day geophilomorph centipedes provide a model system for investigating the evolutionary origins of this diversification, because they exhibit intraspecific variation in segment number. (This variation is, however, derived; it is not a plesiomorphic condition within the Chilopoda.) Previous studies have shown that there are significant differences in segment number between populations within several geophilomorph species. In one (arguably two) species, it has been demonstrated that there is a particular form of geographic patterning of the variation, namely a latitudinal cline, with the segment number decreasing with increasing distance north. Here, we provide additional data on four more species, all of which show evidence of a latitudinal cline in either one or both sexes. It is therefore becoming clear that this is a general phenomenon, applying widely (perhaps universally) across the Geophilomorpha, a group consisting of some 1,000 known species. It may be that latitudinal clines are a frequent part of the speciation cycle in this group.

Latitudinal cline in segment number in an arthropod species, Strigamia maritima.

Arthropods vary more than 30-fold in segment number. The evolutionary origins of differences in segment number among species must ultimately lie in intraspecific variation. Yet paradoxically, in most groups of arthropods, the number of segments is fixed for each species and shows no intra- or interpopulation variation at all. Geophilomorph centipedes are an exception to this general rule, and exhibit intraspecific variation in segment number, with differences between individuals being determined during embryonic development and hence independent of population age structure. Significant differences in segment number between different geographical populations of the same species have been previously reported, but insufficient sampling has been conducted to reveal any particular geographical pattern. Here, we reveal a latitudinal cline in segment number in the geophilomorph species Strigamia maritima: segment number in British populations decreases with distance north. This is the first such cline to be reported for any centipede species; indeed as far as we are aware it is the first such cline reported for any arthropod species. In vertebrates, fish are known to exhibit a latitudinal cline in segment number, but interestingly, this is in the opposite direction; fish add segments with increasing latitude, centipedes subtract them.

Absorbable synthetic versus catgut suture material for perineal repair.

BACKGROUND: Approximately 70% of women will experience some degree of perineal trauma following vaginal delivery and will require stitches. This may result in perineal pain and superficial dyspareunia. OBJECTIVES: The objective of this review was to assess the effects of absorbable synthetic suture material as compared with catgut on the amount of short and long term pain experienced by mothers following perineal repair. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Randomised trials comparing absorbable synthetic (polyglycolic acid and polyglactin) with plain or chromic catgut suture for perineal repair in mothers after vaginal delivery. DATA COLLECTION AND ANALYSIS: Trial quality was assessed independently by two reviewers. Data were extracted by one reviewer and checked by the second reviewer. MAIN RESULTS: Eight trials were included. Compared with catgut, the polyglycolic acid and polyglactin groups were associated with less pain in first three days (odds ratio 0.62, 95% confidence interval 0.54 to 0.71). There was also less need for analgesia (odds ratio 0.63, 95% confidence interval 0.52 to 0.77) and less suture dehiscence (odds ratio 0.45, 95% confidence interval 0.29 to 0.70). There was no significant difference in long term pain (odds ratio 0.81, 95% confidence interval 0.61 to 1.08). Removal of suture material was significantly more common in the polyglycolic acid and polyglactin groups (odds ratio 2.01, 95% confidence interval 1.56 to 2.58). There was no difference in the amount of dyspareunia experienced by women. REVIEWER'S CONCLUSIONS: Absorbable synthetic suture material (in the form of polyglycolic acid and polyglactin sutures) for perineal repair following childbirth appears to decrease women's experience of short-term pain. The length of time taken for the synthetic material to be absorbed is of concern. A trial addressing the use of polyglactin has recently been completed and this has been included in this updated review.

Continuous versus interrupted sutures for perineal repair.

BACKGROUND: Millions of women worldwide undergo perineal repair after childbirth and the type of repair may have an impact on pain and healing. OBJECTIVES: The objective of this review was to assess the effects of continuous subcuticular versus interrupted transcutaneous sutures on women following perineal repair. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. Date of last search: June 1999. SELECTION CRITERIA: Randomised trials comparing continuous subcuticular versus interrupted transcutaneous sutures for the closure of perineal skin after vaginal delivery. DATA COLLECTION AND ANALYSIS: Trial quality was assessed independently by two reviewers. Data were extracted by one reviewer and checked by the second reviewer. Study authors were contacted for additional information. MAIN RESULTS: Four studies involving 1864 women were included. The trials were heterogeneous with respect to operator skill and training. Compared with interrupted sutures, a continuous subcuticular suture technique of perineal repair was associated with less pain for up to 10 days post partum (odds ratio 0.68, 95% confidence interval 0.53 to 0.86). No differences were seen in the need for analgesia, need for resuturing of the wound or in dyspareunia. Based on one trial only, there was no difference in long-term pain and failure to resume pain-free intercourse within three months of the birth. The continuous technique was associated with less need for the removal of sutures. REVIEWER'S CONCLUSIONS: The continuous subcuticular technique of perineal repair may be associated with less pain in the immediate postpartum period than the interrupted suture technique. The long-term effects are less clear.

The effects of the peptide-coupling agent, EEDQ, on 5-HT2A receptor binding and function in rat frontal cortex.

This ex vivo study in rat frontal cortex determined the influence of 5-HT receptor agonists and antagonists on EEDQ-induced depletion of 5-HT2A binding sites and reduction in their functional coupling to phospholipid hydrolysis. Twenty-four hours after EEDQ (6 mg/kg) administration a marked reduction (66%) of cortical 5-HT2A binding sites with no change in binding affinity was observed. The 5HT2A antagonists ritanserin (1 mg/kg), ketanserin (1 and 5 mg/kg), metergoline (3 mg/kg) or the 5HT2A agonist, DOI (3 and 10 mg/kg) also significantly reduced (by 15-44%) these binding sites 24 h after injection. Thirty minute pretreatment with ritanserin, ketanserin, metergoline or DOI (at the doses above) afforded 49-65% protection against the loss of 5-HT2A binding sites induced by EEDQ (6 mg/kg). DOI (10 mg/kg) pretreatment (-24 h) decreased by 26% the accumulation of [3H]inositol phosphates (IPs) evoked by 5-HT (100 microM), but did not affect that produced by DOI (100 microM). Ketanserin (5 mg/kg, -24 h) decreased 5-HT- and DOI-induced IP formation by 65% and 53%, respectively. The EEDQ (6 mg/kg, -24 h)-evoked reductions (-50%) of 5-HT- and DOI-induced IP formation were not altered by DOI (10 mg/kg) or ketanserin (5 mg/kg) given 30 min before EEDQ. G-protein-stimulated IP accumulation was unaffected by EEDQ (6 mg/kg). Overall, EEDQ reduces 5-HT2A binding sites and function in rat frontal cortex, whereas its effects on binding were attenuated by various 5-HT receptor antagonists and agonists, its effects on function was unaltered by these drugs.

D1 receptor binding in rat striatum: modification by various D1 and D2 antagonists, but not by sibutramine hydrochloride, antidepressants or treatments which enhance central dopaminergic function.

[3H]SCH 23390 is a selective high affinity ligand for D1 receptors in vitro. Using this ligand persistent blockade of D1 receptors by SCH 23390 and cis-flupenthixol was shown to significantly increase the number of D1 receptor binding sites in rat striatum. In contrast, repeated administration of the D2-selective antagonist, clebopride, resulted in a small, but significant, reduction in number. No differences in binding affinity were observed and a single dose of these compounds was without effect. The D2-selective antagonist, haloperidol, the non-selective D1/D2 receptor antagonist, chlorpromazine, the dopamine reuptake inhibitors, bupropion, GBR 12909 and nomifensine, and the dopamine releasing agent, d-amphetamine, had no effect on D1 receptors. The antidepressant treatments, desipramine, zimeldine, amitriptyline, tranylcypromine, mianserin and ECS and the monoamine reuptake inhibitor, sibutramine, similarly did not alter striatal D1 sites. Thus, of the treatments investigated only chronic receptor blockade by high affinity antagonists altered D1 receptor binding in rat striatum.