Health state utility values measured using the EuroQol 5-dimensions questionnaire in adults with chronic hepatitis C: a systematic literature review and meta-analysis.

PURPOSE: Chronic hepatitis C infection and its treatment can considerably affect patients' health-related quality-of-life (HRQoL). This study aimed to identify and summarise the current evidence base for health state utility values (HSUVs) in patients with chronic hepatitis C infection, generated using the EuroQol 5-dimensions (EQ-5D) questionnaire. METHODS: MEDLINE, Embase, the Cochrane Library and EconLit were searched from database inception through 31 August 2017. Eligible studies reported HSUVs elicited using the EQ-5D questionnaire in adults with chronic hepatitis C infection. Study quality and risk of bias were assessed. RESULTS: Of 1480 records identified, 26 studies were included. The most commonly defined health states described different stages of chronic hepatitis C infection and specific liver-related disease states, including METAVIR score, compensated and decompensated cirrhosis, hepatocellular carcinoma and liver transplantation. Patients with higher METAVIR scores tended to have lower EQ-5D scores compared to patients with lower METAVIR scores. Patients that achieved sustained virologic responses tended to have higher EQ-5D scores compared to those that did not. A meta-analysis conducted on three studies confirmed that patients with decompensated cirrhosis have significantly lower HSUVs than patients with compensated cirrhosis [mean difference - 0.11 (95% CI - 0.19 to - 0.04)], implying worse HRQoL. However, there was not sufficient evidence to compare how different treatments for chronic hepatitis C infection affect EQ-5D scores. CONCLUSIONS: This study provides a summary of EQ-5D HSUVs for patients with chronic hepatitis C infection, and demonstrates that clinically important disease stages associated with treatment decisions are associated with differences in HRQoL.

An attention and interpretation bias for illness-specific information in chronic fatigue syndrome.

BACKGROUND: Studies have shown that specific cognitions and behaviours play a role in maintaining chronic fatigue syndrome (CFS). However, little research has investigated illness-specific cognitive processing in CFS. This study investigated whether CFS participants had an attentional bias for CFS-related stimuli and a tendency to interpret ambiguous information in a somatic way. It also determined whether cognitive processing biases were associated with co-morbidity, attentional control or self-reported unhelpful cognitions and behaviours. METHOD: A total of 52 CFS and 51 healthy participants completed self-report measures of symptoms, disability, mood, cognitions and behaviours. Participants also completed three experimental tasks, two designed specifically to tap into CFS salient cognitions: (i) visual-probe task measuring attentional bias to illness (somatic symptoms and disability) v. neutral words; (ii) interpretive bias task measuring positive v. somatic interpretations of ambiguous information; and (iii) the Attention Network Test measuring general attentional control. RESULTS: Compared with controls, CFS participants showed a significant attentional bias for fatigue-related words and were significantly more likely to interpret ambiguous information in a somatic way, controlling for depression and anxiety. CFS participants had significantly poorer attentional control than healthy individuals. Attention and interpretation biases were associated with fear/avoidance beliefs. Somatic interpretations were also associated with all-or-nothing behaviour and catastrophizing. CONCLUSIONS: People with CFS have illness-specific biases which may play a part in maintaining symptoms by reinforcing unhelpful illness beliefs and behaviours. Enhancing adaptive processing, such as positive interpretation biases and more flexible attention allocation, may provide beneficial intervention targets.

Early-life hygiene-related factors affect risk of central nervous system demyelination and asthma differentially.

The increasing prevalence of immune-related diseases, including multiple sclerosis, may be partly explained by reduced microbial burden during childhood. Within a multi-centre case-control study population, we examined: (i) the co-morbid immune diseases profile of adults with a first clinical diagnosis of central nervous system demyelination (FCD) and (ii) sibship structure in relation to an autoimmune (FCD) and an allergic (asthma) disease. FCD cases (n = 282) were aged 18-59 years; controls (n = 558) were matched on age, sex and region. Measures include: history of doctor-diagnosed asthma; sibling profile (number; dates of birth); and regular childcare attendance. FCD cases did not differ from controls with regard to personal or family history of allergy, but had a greater likelihood of chronic fatigue syndrome [odds ratio (OR) = 3·11; 95% confidence interval (CI) 1·11, 8·71]. Having any younger siblings showed reduced odds of FCD (OR = 0·68; 95% CI: 0·49, 0·95) but not asthma (OR = 1·47; 95% CI: 0·91, 2·38). In contrast, an increasing number of older siblings was associated with reduced risk of asthma (P trend = 0·04) but not FCD (P trend = 0·66). Allergies were not over-represented among people presenting with FCD. Sibship characteristics influence both FCD and asthma risk but the underlying mechanisms differ, possibly due to the timing of the putative 'sibling effect'.

Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model.

OBJECTIVES: Field-cancerized tissue can give rise to second primary tumours, causing therapeutic failure. Boron neutron capture therapy (BNCT) is based on biological targeting and would serve to treat undetectable foci of malignant transformation. The aim of this study was to optimize BNCT for the integral treatment for oral cancer, with particular emphasis on the inhibitory effect on tumour development originating in precancerous conditions, and radiotoxicity of different BNCT protocols in a hamster cheek pouch oral precancer model. MATERIALS AND METHODS: Groups of cancerized hamsters were locally exposed to single or double (2 or 4 weeks apart) applications of BNCT at different dose levels, mediated by the boron compounds boronophenylalanine (BPA) or BPA and decahydrodecaborate (GB-10) administered jointly. Cancerized, sham-irradiated hamsters served as controls. Clinical status, tumour development from field-cancerized tissue and mucositis were followed for 8 months. RESULTS: A double application (4 weeks apart) of BNCT mediated by GB-10+ BPA at a total dose of 10 Gy in two 5-Gy doses rendered the best therapeutic advantage (63-100% inhibition of tumour development from field-cancerized tissue), minimizing dose-limiting mucositis. CONCLUSION: BNCT can be optimized for the integral treatment for head and neck cancer, considering the implications for field-cancerized tissue.

Epstein-Barr virus and multiple sclerosis.

This review of the considerable evidence linking Epstein-Barr virus (EBV) infection to risk and disease progression in multiple sclerosis (MS) builds on the background to the virus and its interactions with the human host available in the online supplement (see supplement, available online only). The evidence for a similarity in the geographic patterns of occurrence of MS and EBV infection (with infectious mononucleosis or EBV specific serology used as surrogate markers), when reviewed critically, is very limited. There is strong evidence however that people with MS are more likely to report a past history of infectious mononucleosis (thought to represent initial EBV infection at an older age), and higher titres of EBV specific antibodies are associated with an increased risk of developing MS. Elevated levels of the latter are apparent many years before MS onset (compared with non-MS controls) and there is a dose-response relationship between MS risk and antibody titre, with antibodies to the EBV nuclear antigen-1 particularly important. The evidence in relation to EBV DNA load in blood or CSF is conflicting, as is that in relation to T cell responses to EBV. Several hypotheses that have been proposed to explain the links between EBV and MS risk are reviewed and gaps requiring further research are identified.

Association of a dog leukocyte antigen class II haplotype with hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers.

Canine hypoadrenocorticism (Addison's disease) is due to a deficiency of corticosteroids and mineralocorticoids produced by the adrenals. Although this is a relatively uncommon disease in the general dog population, some breeds, including the Nova Scotia Duck Tolling Retriever (NSDTR), are at increased risk for developing hypoadrenocorticism. A prior study has shown that the increased risk is due to a heritable component. This potentially lethal disorder is hypothesized to have an autoimmune etiology, thus the aim of this study was to determine whether genetic susceptibility to hypoadrenocorticism in NSDTRs is associated with genes of the canine major histocompatibility complex [MHC; dog leukocyte antigen system (DLA)]. Samples were collected from NSDTRs diagnosed with hypoadrenocorticism and healthy siblings or country-matched controls. The DLA class II alleles and haplotypes were determined and compared between cases and controls. We found seven different haplotypes of which the haplotype DLA-DRB1*01502/DQA*00601/DQB1*02301 was significantly more prevalent in the diseased dogs (P = 0.044). In addition, these affected dogs also were more likely to be homozygous across the DLA class II region than the control dogs (OR = 6.7, CI = 1.5-29.3, P = 0.011). We also found that homozygous dogs, regardless of their haplotype, tended to have earlier disease onset compared with heterozygous dogs. These data indicate a limited MHC diversity in North American NSDTRs and suggest that the MHC may play a role in the development of hypoadrenocorticism in the NSDTR, supporting the autoimmune origin of the disease.

Childhood infections, vaccinations, and tonsillectomy and risk of first clinical diagnosis of CNS demyelination in the Ausimmune Study.

BACKGROUND: The association between childhood vaccinations and infections and risk of multiple sclerosis is unclear; few studies have considered age at vaccination/infection. OBJECTIVE: To explore age-related associations between childhood vaccinations, infection and tonsillectomy and risk of a first clinical diagnosis of CNS demyelination. METHODS: Data on case (n = 275, 76.6% female; mean age 38.6 years) and age- and sex-matched control (n = 529) participants in an incident population-based case-control study included self-reported age at time of childhood vaccinations, infections, and tonsillectomy. Conditional logistic regression models were used to calculate adjusted odds ratios (AOR) and 95% confidence intervals (CI). RESULTS: Poliomyelitis vaccination prior to school-age was associated with increased risk of a first clinical diagnosis of CNS demyelination (AOR = 2.60, 95%CI 1.02-6.68), based on a very small unvaccinated reference group. Late (11-15 years) rubella vaccination (compared to none) was associated with lower odds of being a case (AOR = 0.47, 95%CI 0.27-0.83). Past infectious mononucleosis at 11-15 years (AOR = 2.84, 95%CI 1.0-7.57) and 16-20 years (AOR = 1.92, 95%CI 1.12-3.27) or tonsillectomy in adolescence (11-15 years: AOR = 2.45, 95%CI 1.12-5.35), including after adjustment for IM, were associated with increased risk of a first clinical diagnosis of CNS demyelination. CONCLUSIONS: Age at vaccination, infection or tonsillectomy may alter the risk of subsequent CNS demyelination. Failing to account for age effects may explain inconsistencies in past findings.

Feasibility of iterative learning control mediated by functional electrical stimulation for reaching after stroke.

BACKGROUND: An inability to perform tasks involving reaching is a common problem following stroke. Evidence supports the use of robotic therapy and functional electrical stimulation (FES) to reduce upper limb impairments, but current systems may not encourage maximal voluntary contribution from the participant because assistance is not responsive to performance. OBJECTIVE: This study aimed to investigate whether iterative learning control (ILC) mediated by FES is a feasible intervention in upper limb stroke rehabilitation. METHODS: Five hemiparetic participants with reduced upper limb function who were at least 6 months poststroke were recruited from the community. No participants withdrew. INTERVENTION: Participants undertook supported tracking tasks using 27 different trajectories augmented by responsive FES to their triceps brachii muscle, with their hand movement constrained in a 2-dimensional plane by a robot. Eighteen 1-hour treatment sessions were used with 2 participants receiving an additional 7 treatment sessions. OUTCOME MEASURES: The primary functional outcome measure was the Action Research Arm Test (ARAT). Impairment measures included the upper limb Fugl-Meyer Assessment (FMA), tests of motor control (tracking accuracy), and isometric force. RESULTS: Compliance was excellent and there were no adverse events. Statistically significant improvements were measured (P

A robotic workstation for stroke rehabilitation of the upper extremity using FES.

An experimental test facility is developed for use by stroke patients in order to improve sensory-motor function of their upper limb. Subjects are seated at the workstation and their task is to repeatedly follow reaching trajectories that are projected onto a target above their arm. To do this they use voluntary control with the addition of electrical stimulation mediated by advanced control schemes applied to muscles in their impaired shoulder and arm. Full details of the design of the workstation and its periphery systems are given, together with a description of its use during the treatment of stroke patients.

A qualitative study exploring views and experiences of people with stroke undergoing transcranial direct current stimulation and upper limb robot therapy.

Background Neurorehabilitation technologies used mainly in research such as robot therapy (RT) and transcranial direct current stimulation (tDCS) can promote upper limb motor recovery after stroke. Understanding the feasibility and efficacy of stroke rehabilitation technologies for upper limb impairments is crucial for effective implementation in practice. Small studies have explored views of RT by people with stroke; however experiences of people receiving tDCS in combination with RT have never been explored. Objective To explore views and experiences of people with sub-acute and chronic stroke that had previously taken part in a randomised controlled trial involving tDCS and RT for their impaired upper limb. Methods An interview study includes open and closed questions. Face-to-face interviews were audio recorded. Open-ended question responses were transcribed and analyzed using thematic analysis; closed questions were analyzed using descriptive analysis. Results Participants felt that RT was enjoyable (90%) and beneficial for their affected arm (100%). From the open question data, it was found that the intervention was effective for the impaired arm especially in the sub-acute stage. Main reported concerns were that tDCS caused painful, itching and burning sensations and RT was sometimes tiring and difficult. Participants recommended that future research should focus on designing a more comfortable method of tDCS and develop a robot that promotes hand movements. Conclusions This study provides new knowledge about the benefits and barriers associated with these technologies which are crucial to the future effective implementation of these tools in practice.

Occupational exposure to power frequency magnetic fields and risk of non-Hodgkin lymphoma.

OBJECTIVES: To investigate the risk of non-Hodgkin lymphoma (NHL) using a job-exposure matrix (JEM) to assess exposure to occupational magnetic fields at the power frequencies of 50/60 Hz. METHODS: The study population consisted of 694 cases of NHL, first diagnosed between 1 January 2000 and 31 August 2001, and 694 controls from two regions in Australia, matched by age, sex and region of residence. A detailed occupational history was given by each subject. Exposure to power frequency magnetic fields was estimated using a population-based JEM which was specifically developed in the United States to assess occupational magnetic field exposure. The cumulative exposure distribution was divided into quartiles and adjusted odds ratios were calculated using the lowest quartile as the referent group. RESULTS: For the total work history, the odds ratio (OR) for workers in the upper quartile of exposure was 1.48 (95% CI 1.02 to 2.16) compared to the referent (p value for trend was 0.006). When the exposure was lagged by 5 years the OR was 1.59 (95% CI 1.07 to 2.36) (p value for trend was 0.003). Adjusting for other occupational exposures did not significantly alter the results. CONCLUSIONS: These findings provide weak support for the hypothesis that occupational exposure to 50/60 Hz magnetic fields increases the risk of NHL.

Factors determining the optimal body site and method for obtaining punch biopsies of human skin as a tissue in which to assess pharmacodynamic and pharmacokinetic endpoints in drug development studies.

There are potential advantages to detecting pharmacodynamic (PD) and pharmacokinetic (PK) endpoints in a tissue-based compartment such as the skin during the development of molecularly targeted drugs. We explored regional differences between inner arm, inner thigh, lower back and buttocks in 12 healthy male Caucasian volunteers in the tolerability of skin biopsy procedures; the Ki67 proliferation index; the frequency of detecting hair follicles and sweat glands; and the percentage of melanocytes. We also explored the amounts of tissue and protein obtained, and two separate methods of splitting biopsies for processing in mutually exclusive media. Biopsies from all body sites were well tolerated. The subjective ranking order was inner arm > buttocks = back > thigh. There were no statistically significant differences in the Ki67 labelling index (P > 0.05). The frequency of detecting sweat glands was the same in all body sites, but the frequency of detecting hair follicles was higher in back and buttock, compared to arm and thigh. The percentage of melanocytes was significantly lower in the buttocks compared to the back and thigh (P < 0.05), but not compared to the arm (P = 0.07). A 4-mm punch biopsy yielded a mean of 16.8 mg of tissue (range: 9-28 mg) and 160 microg of protein (range: 80-270 microg). In vivo sample splitting, by following a 2-mm punch with a 4-mm overpunch, had a shorter time from devascularisation to immersion into processing medium than ex vivo dissection of a 4-mm sample, which may be of importance to the assessment of labile endpoints. We conclude that multiple punch biopsies of the skin are feasible, with the buttocks representing the studied body site with the optimal balance between tolerability, hair follicle density and melanocyte density for obtaining tissue in which to assess PD and PK endpoints during drug development studies.

Upper-limb stroke rehabilitation using electrode-array based functional electrical stimulation with sensing and control innovations.

Functional electrical stimulation (FES) has shown effectiveness in restoring upper-limb movement post-stroke when applied to assist participants' voluntary intention during repeated, motivating tasks. Recent clinical trials have used advanced controllers that precisely adjust FES to assist functional reach and grasp tasks with FES applied to three muscle groups, showing significant reduction in impairment. The system reported in this paper advances the state-of-the-art by: (1) integrating an FES electrode array on the forearm to assist complex hand and wrist gestures; (2) utilising non-contact depth cameras to accurately record the arm, hand and wrist position in 3D; and (3) employing an interactive touch table to present motivating virtual reality (VR) tasks. The system also uses iterative learning control (ILC), a model-based control strategy which adjusts the applied FES based on the tracking error recorded on previous task attempts. Feasibility of the system has been evaluated in experimental trials with 2 unimpaired participants and clinical trials with 4 hemiparetic, chronic stroke participants. The stroke participants attended 17, 1 hour training sessions in which they performed functional tasks, such as button pressing using the touch table and closing a drawer. Stroke participant results show that the joint angle error norm reduced by an average of 50.3% over 6 attempts at each task when assisted by FES.

Multiple sessions of transcranial direct current stimulation and upper extremity rehabilitation in stroke: A review and meta-analysis.

OBJECTIVE: To systematically review the methodology in particular treatment options and outcomes and the effect of multiple sessions of transcranial direct current stimulation (tDCS) with rehabilitation programmes for upper extremity recovery post stroke. METHODS: A search was conducted for randomised controlled trials involving tDCS and rehabilitation for the upper extremity in stroke. Quality of included studies was analysed using the Modified Downs and Black form. The extent of, and effect of variation in treatment parameters such as anodal, cathodal and bi-hemispheric tDCS on upper extremity outcome measures of impairment and activity were analysed using meta-analysis. RESULTS: Nine studies (371 participants with acute, sub-acute and chronic stroke) were included. Different methodologies of tDCS and upper extremity intervention, outcome measures and timing of assessments were identified. Real tDCS combined with rehabilitation had a small non-significant effect of +0.11 (p=0.44) and +0.24 (p=0.11) on upper extremity impairments and activities at post-intervention respectively. CONCLUSION: Various tDCS methods have been used in stroke rehabilitation. The evidence so far is not statistically significant, but is suggestive of, at best, a small beneficial effect on upper extremity impairment. SIGNIFICANCE: Future research should focus on which patients and rehabilitation programmes are likely to respond to different tDCS regimes.

The effects of simultaneous or separate infusions of some pro-opiomelanocortin-derived peptides (beta-endorphin, melanocyte stimulating hormone, and corticotrophin-like intermediate polypeptide) and their acetylated derivatives upon sexual and ingestive behaviour of male rats.

Intraneuronal post-translational cleavage of pro-opiomelanocortin yields a variety of peptides including beta-endorphin, melanocyte stimulating hormone and corticotrophin-like intermediate polypeptide, some of which are subsequently N-acetylated. Such peptides may be co-released from neuronal terminals, and so these experiments explored the effects of co-administration of some of them on sexual behaviour in the male rat, which is known to be sensitive to hypothalamic infusions of beta-endorphin. Peptides were infused into the pre-optic-anterior hypothalamic area bilaterally in doses up to 320 pmol, and males allowed access to a sexually receptive female and/or a sweet solution (0.1% Acesulfame-K) for 15 min, so that both sexual and ingestive behaviour could be studied. beta-Endorphin(1-31) by itself inhibited sexual interaction, confirming our previous data. Acesulfame-K ingestion was inhibited in control-infused rats in the presence of a female, but this inhibition was released when sexual behaviour was itself diminished by beta-endorphin(1-31). Both the acetylated and non-acetylated forms of melanocyte stimulating hormone (alpha-melanocyte stimulating hormone and des-acetyl melanocyte stimulating hormone) stimulate sexual behaviour; latencies both to ejaculation and to resumption of copulatory behaviour after an ejaculation (post-ejaculatory interval) were reduced. However, infusion of either corticotrophin-like intermediate peptide or N-acetylated beta-endorphin (1-31) had no effect on either sexual or ingestive behaviour. Infusion of either acetylated melanocyte stimulating hormone or des-acetyl melanocyte stimulating hormone mixed with beta-endorphin(1-31) prevented the inhibitory effect of the latter on sexual behaviour. Dose-response studies showed that the behavioural effect of such mixtures depended upon the molar ratios of the two peptides, rather than their absolute concentrations. The higher the ratio in favour of alpha-melanocyte stimulating hormone or des-acetyl melanocyte stimulating hormone, the greater the display of sexual behaviour. Infusing either corticotrophin-like intermediate polypeptides or N-acetyl beta-endorphin(1-31) with beta-endorphin(1-31) did not prevent the inhibition of sexual activity expected with beta-endorphin(1-31) alone. These results are discussed in terms of the functional consequences of co-release of proopiomelanocortin peptides from hypothalamic nerve terminals.

Selective effects of beta-endorphin infused into the hypothalamus, preoptic area and bed nucleus of the stria terminalis on the sexual and ingestive behaviour of male rats.

beta-Endorphin was infused bilaterally into the medial preoptic area-anterior hypothalamic continuum at doses of 5, 10 and 40 pmol each side. The highest dose selectively abolished mounting, intromitting and ejaculating in sexually experienced male rats paired with an oestrous female. Males infused with 40 pmol beta-endorphin still followed the female, investigated her anogenital region and other parts of her body, but made abortive attempts to mount. A dose of 5 pmol beta-endorphin had no effect, but 10 pmol proved partially effective. The same males, in other tests, were allowed to ingest a highly preferred, sweet, non-calorific solution (acesulfame-K) in the absence of a female. beta-Endorphin infusions (up to 40 pmol) into the same area of the hypothalamus had no effect on this behaviour. Control males allowed simultaneous access both to an oestrous female and to the sweet solution copulated normally but reduced their ingestive behaviour, despite there being sufficient time during tests for both to occur. beta-Endorphin (40 pmol) infused into the preoptic area-anterior hypothalamic continuum under these conditions suppressed sexual interaction, but ingestion of acesulfame-K increased to values observed when the female was absent. beta-Endorphin infused into neighbouring areas of the brain had different behavioural effects. Sexual behaviour was not inhibited, and ingestion of acesulfame-K was unaltered, when beta-endorphin was infused either into the bed nucleus of the stria terminalis or the rostral ventromedial hypothalamus. However, infusions of cholecystokinin-8 into the ventromedial hypothalamus suppressed acesulfame-K ingestion in most animals, showing that the cannulae were placed in an area regulating ingestive behaviour. The inhibition of sexual behaviour after preoptic area-anterior hypothalamic continuum infusions of beta-endorphin was prevented by either pretreating rats with 1 mg/kg naloxone intraperitoneally, or by infusing a putative delta opiate receptor blocker (0.5 pmols ICI 174864) into the preoptic area-anterior hypothalamic continuum 5 min prior to beta-endorphin treatment. ICI 174864 administered alone significantly increased mount rate and reduced the post-ejaculatory refractory period in copulating males. These experiments suggest that there is both neurochemical and neuroanatomical specificity relating beta-endorphin to sexual behaviour in the male rat.

Cytocidal effect of rifamycin derivatives on ascites tumor cells: studies with [125I]iododeoxyuridine.

The cytotoxicity of 2 rifamycin derivatives, rifazone-82 and rifampicin, on mouse ascites cells was studied, using the [125I]iododeoxyuridine (IUDR) method of labeling the tumor cells. This technique allows a distinction to be made between a cytocidal and cytostatic effect. The 2 drugs exerted a cytocidal effect against 2 non-leukemic cell lines, but had no effect against 3 leukemic lines.

Effect of some rifamycin derivatives on chemically-induced mammary tumors in rats.

Five rifamycin derivatives have been compared for their effectiveness in inhibiting chemically-induced mammary tumours in rats. Daily oral administration of DMB (dimethylbenzyl-desmethylrifampicin), starting 2 weeks before the carcinogen challenge, was the most effective, both in inhibiting or delaying the onset of tumours and in slowing the growth of those that occurred. The inhibitory effects of rifampin, dirifampin, RC-16(rifazacyclo16) and R-82) were less than those of DMB when administered by the same route at the same dose level.

Comparative effects of preoptic area infusions of opioid peptides, lesions and castration on sexual behaviour in male rats: studies of instrumental behaviour, conditioned place preference and partner preference.

The effects on the sexual behaviour of male rats of excitotoxic amino acid-induced lesions of the medial preoptic area-anterior hypothalamic area (mPOA/AHA), infusions of beta-endorphin, alpha-melanocyte stimulating hormone and naloxone into the mPOA/AHA, systemic naloxone and castration were compared using different behavioural paradigms. These included measures of unconditioned copulatory behaviour, instrumental responses for an oestrous female presented under a second-order schedule of reinforcement, conditioned place preference and partner preference. The results demonstrate that manipulations of the mPOA/AHA markedly affect consummatory aspects of sexual behaviour (mounting, intromitting and ejaculating) but tend not to affect appetitive or reward-related aspects of sexual behaviour, although intra-mPOA/AHA alpha MSH did result in a small increase in instrumental responses, while beta-endorphin infused into the mPOA/AHA also abolished preference for an oestrous over an anoestrous female. Systemic naloxone, on the other hand, reduced instrumental behaviour and a place preference conditioned by prior sexual interaction, while the same compound infused into the mPOA/AHA markedly facilitated copulatory responses but did not affect other measures of appetitive sexual responses. Castration caused an extremely rapid attenuation of conditioned place preference which was apparent before the males had experienced reductions in their copulatory performance. This treatment only slowly reduced partner preference. The results indicate that the use of several behavioural procedures can reveal discrete actions of neuroendocrine treatments on separable psychological processes which underly the integrated pattern of masculine sexual behaviour. In particular, they suggest that the mPOA/AHA is especially concerned with the copulatory responses of mounting and intromitting, but is much less important for a variety of appetitive sexual acts as well as sexual reward, as measured in the place preference procedure. The marked effects of castration on conditioned place preference taken together with the lack of effect of lesions of the mPOA/AHA on this measure indicate that testosterone affects sexual reward-related processes by an action at a site other than the mPOA/AHA. The implications of these findings are discussed.

Oxytocin in the central nervous system and sexual behaviour in male rats.

Concentrations of oxytocin (OT) and vasopressin (AVP) were measured in cerebrospinal fluid (CSF) obtained from the cisterna magna of freely moving rats. Basal levels of OT and AVP were approximately 9 fmol/ml in both male and female. In the male rats this increased to approximately 18 fmol/ml 5 min after ejaculation, and 27 fmol/ml 20 min after ejaculation. No increase from basal levels occurred when males were placed with unreceptive females, or alone in the test environment. AVP levels were unchanged in any condition. Preliminary investigations indicate that discrete electrolytic lesions to the lateral and posterior parvocellular hypothalamic paraventricular nucleus (PVN) abolished this ejaculation-associated increase in CSF OT, prolonged mount and intromission latencies and reduced the absolute postejaculatory interval (PEI). We conclude that intracerebrally projecting OT systems may be activated during coitus and may contribute to the mechanisms underlying postejaculatory refractoriness.