Tetanus prophylaxis in horses: guidelines for New Zealand and Australia based on a critical appraisal of the evidence.

Horses are exquisitely sensitive to tetanus neurotoxin and are exposed to the risk of infection with Clostridium tetani throughout life. The vaccine against tetanus is highly effective at preventing disease, whereas tetanus in unvaccinated populations is associated with high mortality rates. Current guidelines in New Zealand and Australia for the available vaccine contain contradictions and limitations surrounding the optimal tetanus immunisation protocols for both adult horses and foals. This review critically evaluates the scientific literature on tetanus prophylaxis in horses within the context of equine practice and available products in New Zealand and Australia. The review was conducted by a panel of industry and specialist veterinarians to obtain agreement on nine equine tetanus prophylaxis guidelines for practising veterinarians. The primary protocol for tetanus toxoid (TT) immunisation consists of a three-dose series IM for all horses ≥ 6 months of age, and a four-dose series IM is proposed if commencing vaccination in foals between 3 and 6 months of age. Tetanus prophylaxis in foals < 3 months of age relies on passive immunity strategies. Following the completion of the primary protocol, a TT booster dose IM should be administered within 5 years, and every 5 years thereafter. When followed, these protocols should provide adequate protection against tetanus in horses. Additional tetanus prophylaxis guidelines are provided for veterinarians attending a horse experiencing a known "risk event" (e.g. wound, hoof abscess, surgery, umbilical infection). When a correctly vaccinated horse experiences a risk event, pre-existing immunity provides protection against tetanus. When an unvaccinated horse or one with unknown vaccination status, or a foal born to an unvaccinated dam, experiences a risk event, TT IM and tetanus antitoxin (TAT) 1,500 IU SC should be administered simultaneously at separate sites, and the TT primary immunisation protocol should subsequently be completed for the horse's respective age. In previously immunised pregnant broodmares, a TT booster dose administered 4-8 weeks prior to parturition optimises the transfer of passive immunity against tetanus to the newborn foal via colostrum; provided that post-natal IgG concentration in serum is > 800 mg/dL (8 g/L), such foals should be passively protected against tetanus up to 6 months of age. Survivors of clinical tetanus must still receive the primary protocol for vaccination against tetanus. In summary, all horses in New Zealand and Australia should be vaccinated against tetanus with protection maintained throughout life via TT booster doses, facilitated by accurate medical record keeping and client education.

Examining the associations between self and body compassion and health related quality of life in people diagnosed with endometriosis.

OBJECTIVE: An understanding of the role that self and body compassion may play as protective mechanisms in the context of psychological and physical health conditions is steadily increasing. The availability of research pertaining to their role in mitigating the health-related quality of life (HRQoL) impacts associated with endometriosis is limited. The current study examined the influence of self and body compassion on HRQoL in people diagnosed with endometriosis. METHODS: Individuals aged 18+ years (n = 318), assigned female at birth, with a self-reported diagnosis of symptomatic endometriosis completed an online cross-sectional survey. Participant demographics and endometriosis-related data was collected in addition to self and body compassion and HRQoL. Standard multiple regression analyses (MRA) were conducted to estimate the proportion of variance in HRQoL that can be accounted for by self and body compassion in endometriosis. RESULTS: Self and body compassion were both associated with higher HRQoL across all domains. However, when both self and body compassion were entered into a regression, only body compassion was significantly associated with HRQoL domains of physical wellbeing, bodily pain, vitality, social engagement and general HRQoL; self-compassion explained no unique variance. In the domain of emotional wellbeing, when both self and body compassion were entered into a regression, both were significantly associated, and explained unique variance. CONCLUSIONS: It is suggested that future psychological interventions for individuals living with endometriosis should emphasise building general self-compassionate abilities with a subsequent specific focus on strategies designed to improve body compassion.

Predictors of self-compassion in endometriosis: the role of psychological health and endometriosis symptom burden.

STUDY QUESTION: What is the relationship between self-compassion, endometriosis-related symptoms and psychological health in women with symptomatic endometriosis? SUMMARY ANSWER: Decreased self-compassion is associated with increased psychological distress, extended diagnostic delay and varies according to individual endometriosis-symptom profile. WHAT IS KNOWN ALREADY: Existing research indicates that endometriosis is associated with reduced psychological health and varied endometriosis-related symptom profiles. Examining the level of self-compassion reported by women with endometriosis is important as greater self-compassion has been found to improve psychological well-being in several chronic health populations. STUDY DESIGN, SIZE, DURATION: This study utilized a cross-sectional survey design to explore the relationship between self-compassion, psychological health and endometriosis-related symptoms (n = 318). PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with a self-reported diagnosis of endometriosis were recruited via online advertising through social media platforms. Demographic and endometriosis-specific information (e.g. disease stage, diagnostic delay, symptom experience) was collected in addition to psychological health and self-compassion. Psychological health was measured by the PROMIS Emotional Distress and Anxiety short forms and the Patient Health Questionnaire (PHQ-15). Self-compassion was measured by the Self-Compassion Scale (26-item). Independent t-tests, bivariate correlations and linear regression analyses explored the relationship between specific endometriosis-related symptoms, psychological health and self-compassion. MAIN RESULTS AND THE ROLE OF CHANCE: Hierarchical multiple regression indicated that psychological symptoms accounted for the greatest variance in levels of self-compassion in the current sample. Depression and anxiety were found to be significant negative predictors of self-compassion. Notable symptoms that were significant in the final model were the presence of dysmenorrhea, lower back pain, dyspareunia, pain after sexual intercourse, fatigue and nausea. LIMITATIONS, REASONS FOR CAUTION: The cross-sectional nature of the findings prevents direct findings of causality. The information pertaining to endometriosis was self-report in nature and was not medically verified. WIDER IMPLICATIONS OF THE FINDINGS: These preliminary findings indicate the importance of clinical interventions aimed at enhancing self-compassion and the importance of individual case conceptualization and treatment planning based on endometriosis-related symptomatic profiles. STUDY FUNDING/COMPETING INTEREST(S): The study was not associated with research funding. Author L.V.N. is a member of the Endometriosis Australia Clinical Advisory Committee. TRIAL REGISTRATION NUMBER: N/A.

Extended role of transnasal oesophagoscopy: a review of the literature.

BACKGROUND: Advances in endoscopic technology have allowed transnasal oesophagoscopy to be used for a variety of diagnostic and therapeutic procedures. METHOD: A review of the literature was carried out to look into the extended role of transnasal oesophagoscopy within otolaryngology, using the Embase, Cinahl and Medline databases. RESULTS: There were 16 studies showing that transnasal oesophagoscopy is safe and cost effective and can be used for removal of foreign bodies, tracheoesophageal puncture, laser laryngeal surgery and balloon dilatation. CONCLUSION: This study presents a summary of the literature showing that transnasal oesophagoscopy can be used as a safe and cost-effective alternative or adjunct to traditional rigid endoscopes for therapeutic procedures.

Evidence-based treatment of multicystic dysplastic kidney: a systematic review.

OBJECTIVES: There is a lack of a standardised protocol for the investigation and non-operative management of paediatric multicystic dysplastic kidney (MCDK). Institutional protocols for non-operative management remain essentially ad hoc. The primary outcome of this systematic review is to establish the incidence of hypertension associated with an MCDK. The secondary outcome is to determine the malignancy risk associated with an MCDK. The tertiary outcome is to assess the rate of MCDK involution. Subsequent to these, an evidence-based algorithm for follow-up is described. METHODOLOGY: A systematic review of all relevant studies published between 1968 and April 2017 was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were identified by specific inclusion and exclusion criteria, all of which included data relevant to the primary, secondary and tertiary outcomes. Hypertension was defined as systolic blood pressure greater than the 95th centile for gender, age and height centile. Subset analysis was performed for hypertension associated with an MCDK. RESULTS: The primary outcome measure revealed a 3.2% (27/838) risk of developing hypertension associated with an MCDK. The secondary outcome measure noted a 0.07% malignancy risk (2/2820). The tertiary outcome measure established that 53.3% (1502/2820) had evidence of involution of the dysplastic kidney. A total of 44 cohort studies (2820 patients) were analysed. CONCLUSION: Given the low risk of hypertension and malignancy, which is similar to the general population, the current conservative non-operative pathway is an appropriate management strategy. An algorithm to help support clinicians with ongoing management is proposed.

Retrospective Evaluation of Horses Diagnosed with Neuroborreliosis on Postmortem Examination: 16 Cases (2004-2015).

BACKGROUND: Equine neuroborreliosis (NB), Lyme disease, is difficult to diagnose and has limited description in the literature. OBJECTIVE: Provide a detailed description of clinical signs, diagnostic, and pathologic findings of horses with NB. ANIMALS: Sixteen horses with histologically confirmed NB. METHODS: Retrospective review of medical records at the University of Pennsylvania and via an ACVIM listserv query with inclusion criteria requiring possible exposure to Borrelia burgdorferi and histologic findings consistent with previous reports of NB without evidence of other disease. RESULTS: Sixteen horses were identified, 12 of which had additional evidence of NB. Clinical signs were variable including muscle atrophy or weight loss (12), cranial nerve deficits (11), ataxia (10), changes in behavior (9), dysphagia (7), fasciculations (6), neck stiffness (6), episodic respiratory distress (5), uveitis (5), fever (2), joint effusion (2), and cardiac arrhythmias (1). Serologic analysis was positive for B. burgdorferi infection in 6/13 cases tested. CSF abnormalities were present in 8/13 cases tested, including xanthochromia (4/13), increased total protein (5/13; median: 91 mg/dL, range: 25-219 mg/dL), and a neutrophilic (6/13) or lymphocytic (2/13) pleocytosis (median: 25 nucleated cells/µL, range: 0-922 nucleated cells/µL). PCR on CSF for B. burgdorferi was negative in the 7 cases that were tested. CONCLUSION AND CLINICAL IMPORTANCE: Diagnosis of equine NB is challenging due to variable clinical presentation and lack of sensitive and specific diagnostic tests. Negative serology and normal CSF analysis do not exclude the diagnosis of NB.

Four pediatric patients with autosomal recessive polycystic kidney disease developed new-onset diabetes after renal transplantation.

NODAT is increasingly prevalent. Compared with adult recipients, NODAT is less prevalent in pediatric renal transplant recipients; however, some risk factors for its development in young patients have been defined. We report four pediatric renal transplant recipients with ARPKD who developed NODAT. We review the current pediatric NODAT literature and hypothesize that ARPKD may be an additional risk factor for NODAT.

Flow-mediated K(+) secretion in horses intoxicated with lolitrem B (perennial ryegrass staggers).

AIM: To investigate the effects of lolitrem B intoxication on renal K(+) secretion in response to increased tubular flow rates. METHODS: Results are derived from a repeated measure pilot study of seven horses fed non-perennial ryegrass feed for a week prior to exposing them to perennial ryegrass seed and hay that contained an average of 2 ppm lolitrem B. At the end of the control and treatment period frusemide (1 mg/kg I/V) was administered and serial fractional excretion of K(+)(FEK(+)) and fractional excretion of Na(+)(FENa(+)) calculated. Baseline concentration of aldosterone in plasma, serum K(+)concentration and feed K(+) concentration were also compared. RESULTS: Key findings included a reduced change in FEK(+) from 0 to 15 minutes in response to frusemide administration (p=0.022, Wilcoxon signed-rank test) and a reduced baseline concentration of aldosterone in plasma (p=0.022, Wilcoxon signed-rank test) during the treatment period compared with the control. CONCLUSIONS: Results suggest that lolitrem B intoxication reduced flow-mediated K(+) secretion and interfered with aldosterone production or secretion. However, further investigation is required to validate these findings and to further elucidate the underlying pathophysiology. CLINICAL RELEVANCE: Lolitrem B intoxication in horses may cause disruption to electrolyte handling in addition to neurological deficits.

Fasting blood glucose and insulin sensitivity are unaffected by HAART duration in Cameroonians receiving first-line antiretroviral treatment.

AIMS: This study assessed the relationship between highly active antiretroviral therapy (HAART) duration and cardiometabolic disorders in HIV-infected Cameroonians. METHODS: HIV-infected Cameroonians aged 21 years or above were cross-sectionally recruited at the Yaoundé Central Hospital, a certified HIV care centre, and their anthropometry, body composition (impedancemetry), fasting blood glucose (FBG) and lipid levels, and insulin sensitivity (IS; short insulin tolerance test) were measured. RESULTS: A total of 143 participants with various durations of HAART [treatment-naïve (n=28), 1-13 months (n=44), 14-33 months (n=35) and 34-86 months (n=36)] were recruited. They were mostly women (72%), and had a mean age of 39.5 (SD: 9.8) years. Half (52%) were using a stavudine-containing regimen. There was a significant trend towards a positive change in body mass index and waist-to-hip ratio with increasing duration of HAART (all P=0.02). Systolic (P=0.04) and diastolic (P=0.03) blood pressure, total cholesterol (P=0.01), prevalence of hypertension (P=0.04) and hypercholesterolaemia (P=0.007) were also significantly increased with HAART duration, whereas triglycerides, FBG and IS were unaffected. Clustering of metabolic disorders increased (P=0.02 for ≥1 component of the metabolic syndrome and P=0.09 for ≥2 components) with HAART duration. CONCLUSION: HAART duration is associated with obesity, fat distribution, blood pressure and cholesterol levels in HIV-infected Cameroonians, but does not appear to significantly affect glucose metabolism.

Clinical expression of lolitrem B (perennial ryegrass) intoxication in horses.

REASONS FOR PERFORMING STUDY: Perennial ryegrass staggers is purported to be a common neurological mycotoxicosis of horses but the case description lacks detail and evidence. OBJECTIVE: To describe the clinical syndrome of lolitrem B intoxication in horses, limiting tests to those that are applicable to clinical practice, and to assess the potential value of enzyme-linked immunosorbent assay (ELISA) tests for lolitrem B in horse body fluids. METHODS: Seven horses in 2 separate groups were fed perennial ryegrass seed and hay containing 2 ppm lolitrem B. Paired data were collected prior to and after 2 weeks exposure to lolitrem B, including video-documented neurological examination and clinical examination. RESULTS: All horses developed a variable degree of tremor and ataxia when exposed to lolitrem B. Tremor depended on the level of activity and included a subtle, rapid tremor of the eyeball. Ataxia was exaggerated by blindfolding and primarily involved a truncal sway and irregular, but predictable, limb placements. No change was detected in urine lolitrem B levels and, although plasma lolitrem B increased during the treatment period, levels did not correlate with the severity of clinical signs displayed. Limb swelling, heel lesions and serous nasal discharge were also observed in horses most severely intoxicated. CONCLUSIONS: The clinical effects of lolitrem B intoxication in horses primarily involve action-related tremors and symmetrical vestibular ataxia. Ergovaline may have caused the limb swelling, heel lesions and serous nasal discharge. Plasma ELISA for lolitrem B may be of diagnostic use in the future. POTENTIAL RELEVANCE: This study provides a clearer appreciation of the clinical signs and variability of perennial ryegrass intoxication in horses.

Nucleotide sequence of Pseudomonas aeruginosa conjugative plasmid pUM505 containing virulence and heavy-metal resistance genes.

We determined the complete nucleotide sequence of conjugative plasmid pUM505 isolated from a clinical strain of Pseudomonas aeruginosa. The plasmid had a length of 123,322bp and contained 138 complete coding regions, including 46% open reading frames encoding hypothetical proteins. pUM505 can be considered a hybrid plasmid because it presents two well-defined regions. The first region corresponded to a larger DNA segment with homology to a pathogenicity island from virulent Pseudomonas strains; this island in pUM505 was comprised of genes probably involved in virulence and genes encoding proteins implicated in replication, maintenance and plasmid transfer. Sequence analysis identified pil genes encoding a type IV secretion system, establishing pUM505 as a member of the family of IncI1 plasmids. Plasmid pUM505 also contained virB4/virD4 homologues, which are linked to virulence in other plasmids. The second region, smaller in length, contains inorganic mercury and chromate resistance gene clusters both flanked by putative mobile elements. Although no genes for antibiotic resistance were identified, when pUM505 was transferred to a recipient strain of P. aeruginosa it conferred resistance to the fluoroquinolone ciprofloxacin. pUM505 also conferred resistance to the superoxide radical generator paraquat. pUM505 could provide Pseudomonas strains with a wide variety of adaptive traits such as virulence, heavy-metal and antibiotic resistance and oxidative stress tolerance which can be selective factors for the distribution and prevalence of this plasmid in diverse environments, including hospitals and heavy metal contaminated soils.

The suppression of gastro-oesophageal reflux by alginates.

AIMS: The aim of this study was to compare alginate products with the same amount of active ingredients but different dosage forms, in the suppression of reflux provoked by a standard meal in healthy human volunteers, using ambulatory oesophageal pH monitoring. METHODS: This was a single centre, randomised, open, three-period crossover, controlled study comparing Gaviscon Advance (10 ml) with a control (10 ml water) and with a new tablet product containing the same active ingredients as Gaviscon Advance. Volunteers who had oesophageal pH < 4 for at least 2% of the 4-h period after ingestion of a test meal followed by control at a reflux screening visit were included in the study. RESULTS: The difference between Gaviscon Advance and control in the mean angular transformed percentage of time for which oesophageal pH fell below four was statistically significant (p < 0.0001) demonstrating the sensitivity of the method. No significant difference between the two alginate products was found based on the least squares adjusted mean angular transformed percentage of time for which pH fell below four. There were also no significant differences between the two alginate dosage forms in the angular transformed percentage of time for which oesophageal pH fell below five and in the log-transformed number of occasions on which oesophageal pH fell below four and five. DISCUSSION AND CONCLUSION: The study shows that alginate reflux suppressants containing a low amount of antacid are effective in suppressing acid reflux and that suspension and tablet forms are able to give equivalent acid suppression.

Effects of neurotensin on the organization of activity in supraoptic nucleus cells in virgin and lactating rats.

Neurotensin increases the firing rate of supraoptic nucleus oxytocin and vasopressin neurones in vitro and induces Fos protein expression in the supraoptic nucleus in vivo. Here, we used extracellular single-unit electrophysiological recording combined with local microdialysis administration of neurotensin (1 mM at 2 micro l/min) to investigate the effects of locally applied neurotensin on the firing of oxytocin and vasopressin neurones in urethane-anaesthetized virgin and lactating rats. Neurotensin decreased the mean firing rate of oxytocin cells in virgin, but not lactating, rats. In addition, neurotensin increased the index of dispersion (a measure of the variability of firing) in virgin, but not lactating, rats. By contrast to oxytocin cells, neurotensin increased the mean firing rate of vasopressin cells in both virgin and lactating rats, but did not alter the index of dispersion. The increase in firing of phasic vasopressin cells was achieved through an increase in intraburst frequency (rather than an increase in burst duration or decrease in interburst interval), which resulted from a reduction of the spike-frequency adaptation that develops over the course of phasic bursts. Thus, neurotensin has differential effects on activity patterning in oxytocin and vasopressin cells and the effects on oxytocin cells, but not vasopressin cells, depend upon the physiological status of the animal. The increase in the variability of firing of oxytocin cells induced by neurotensin in virgin rats, but not in lactating rats, suggests that neurotensin (or other neurotransmitters/neuromodulators with similar actions) might establish conditions that predispose oxytocin cells to fire in milk-ejection bursts in lactating rats.

Food intake and leptin during pregnancy and lactation.

Successful reproduction requires the accumulation of energy reserves. Although acute and chronic food deprivation disrupts reproduction, surprisingly, an over-abundance of energy reserves can also result in infertility. The infertility of obese, ob/ob mice can be reversed by the reintroduction of leptin, the protein product of the ob gene. In rats, energy reserves are increased during pregnancy by far accumulation and during lactation by hyperphagia. We have therefore investigated the interactions of leptin and food intake during late pregnancy and lactation in rats. Cycling rats consume their daily food intake during the dark phase and this is accompanied by a subsequent increase in plasma leptin concentration compared to light levels. During late pregnancy, rats increase their food intake during the dark phase and this is accompanied by a nocturnal increase in plasma leptin level. However, the nocturnal increase is not seen on the day prior to parturition, and is absent throughout lactation. Surprisingly, despite the massive increase in food intake during lactation plasma leptin levels continue to fall, suggesting that leptin release in response to food intake is suppressed during lactation. Furthermore, central leptin administration is less effective in reducing food intake in late pregnant and early lactating rats compared to cycling rats which suggests that these rats are insensitive to leptin. This may result from downregulation of brain leptin receptors. Decreased leptin production and action during late pregnancy and lactation will result in a decreased satiety effect, with up-regulation of orexigenic factors that produce hyperphagia, so allowing adequate energy intake for successful rearing of offspring.

Effect of suckling on NADPH-diaphorase (Nitric oxide synthase, NOS) reactivity and NOS gene expression in the paraventricular and supraoptic nuclei of lactating rats.

This study examined the effect of suckling on nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d, a histochemical marker for nitric oxide synthase, NOS) reactivity and neuronal NOS mRNA expression in the paraventricular (PVN) and supraoptic (SON) nuclei of lactating rats. Freely nursing (non-separated) dams and those separated from pups for 12 h and then reunited for 0, 15, 30, 60, 90, 120 and 180 min were used for the study. Dams separated from pups and sacrificed at time zero (without reunion) showed a significant decrease in NADPH-d staining and NADPH-d positive cells as well as in the NOS mRNA expression in the PVN and SON compared to that observed in non-separated dams. Reunion with pups and restoration of suckling significantly increased NADPH-d reactivity after 15, 30, 60 min, but not after 90, 120 and 180 min compared to non-reunited pups-deprived dams. A pattern of NADPH-d reactivity and neuronal NOS mRNA expression indistinguishable from that observed during free lactation was reinstated shortly (15 min) after the restoration of suckling stimulus, suggesting that the NADPH-d reactivity in lactation depends on the presence of the suckling stimulus. These results show that suckling stimulus may play a modulatory role in the regulation of NOS reactivity in the magnocellular neurones of the hypothalamic PVN and SON during lactation.

Local injection of pertussis toxin attenuates morphine withdrawal excitation of rat supraoptic nucleus neurones.

Morphine inhibits oxytocin neurones via G(i/o)-protein-linked mu-opioid receptors. Following chronic morphine administration oxytocin cells develop dependence, shown by withdrawal excitation after administration of the opioid antagonist, naloxone. Here, inactivation of G(i/o)-proteins by pre-treatment of morphine-dependent rats with pertussis toxin injected into the left supraoptic nucleus reduced withdrawal-induced Fos protein expression within the injected nucleus by 41+/-10% compared to the contralateral nucleus, indicating that functional G(i/o)-proteins are essential for the development and/or expression of morphine dependence by oxytocin cells in the supraoptic nucleus. In another group of rats, pertussis toxin did not alter the responses to either systemic cholecystokinin administration or systemic hypertonic saline administration, indicating that pertussis toxin does not prevent oxytocin cells from responding to stimuli that are not mediated by G(i/o)-proteins. Finally, pertussis toxin reduced acute morphine inhibition of systemic hypertonic saline-induced Fos protein expression in the supraoptic nucleus, confirming that pertussis toxin effectively inactivates G(i/o)-proteins in the supraoptic nucleus. Thus, the expression of morphine withdrawal excitation by supraoptic nucleus oxytocin cells requires the functional integrity of G(i/o)-proteins within the nucleus.

Local morphine withdrawal increases c-fos gene, Fos protein, and oxytocin gene expression in hypothalamic magnocellular neurosecretory cells.

We measured stimulation of c-fos and oxytocin gene expression during excitation of oxytocin cells induced by systemic or local morphine withdrawal. Female rats were made morphine-dependent by intracerebroventricular morphine infusion over 5 d. Morphine withdrawal, induced by systemic injection of the opioid antagonist naloxone (5 mg/kg) in conscious or anesthetized rats, increased the density of c-fos messenger RNA and of oxytocin heterogeneous nuclear RNA in supraoptic nucleus cells compared with those of nonwithdrawn rats; c-fos messenger RNA was also increased in the magnocellular and parvocellular paraventricular nuclei of withdrawn rats. Morphine withdrawal increased the number of Fos-immunoreactive cells in the supraoptic and magnocellular paraventricular nuclei of conscious or pentobarbitone-anesthetized rats. Morphine withdrawal also increased Fos-immunoreactive cell numbers in the parvocellular paraventricular nucleus of conscious but not anesthetized rats. Central administration of the alpha(1)-adrenoreceptor antagonist benoxathian (5 microg/min) did not prevent morphine withdrawal-induced increases in the numbers of Fos-immunoreactive neurons in the supraoptic or magnocellular paraventricular nucleus. Unilateral microdialysis administration of naloxone (10(-5) M) into the supraoptic nucleus of anesthetized morphine-dependent rats increased Fos-immunoreactive cell numbers compared with the contralateral nucleus. Finally, we investigated whether dependence could be induced by chronic unilateral infusion of morphine into a supraoptic nucleus; systemic naloxone (5 mg/kg) increased Fos-immunoreactive cell numbers in the morphine-infused nucleus compared with the contralateral nucleus. Thus, morphine withdrawal excitation increases c-fos and oxytocin gene expression in supraoptic nucleus neurons. This occurs independently from excitation of their ascending noradrenergic inputs, and both dependence and withdrawal can be induced within the supraoptic nucleus.