Same-sex sexual behaviour among mammals is widely observed, yet seldomly reported: Evidence from an online expert survey.

Same-sex sexual behaviour (SSSB) occurs in most animal clades, but published reports are largely concentrated in a few taxa. Thus, there remains a paucity of published reports for most mammalian species. We conducted a cross-sectional expert survey to better understand the underlying reasons for the lack of publications on this topic. Most respondents researched Primates (83.6%, N = 61), while the rest studied Carnivora (6.9%, N = 5), Rodentia (4.1%, N = 3), Artiodactyla (2.7%, N = 2), and Proboscidea (2.7%, N = 2). Most respondents (76.7%, N = 56) had observed SSSB in their study species, but only 48.2% (N = 27) collected data on SSSB, and few (18.5%, N = 5) had published papers on SSSB. Of the unique species identified as engaging in SSSB in the survey, 38.6% (N = 17) have no existing reports of SSSB to the knowledge of the authors. In both the survey questions and freeform responses, most respondents indicated that their lack of data collection or publication on SSSB was because the behaviours were rare, or because it was not a research priority of their lab. No respondents reported discomfort or sociopolitical concerns at their university or field site as a reason for why they did not collect data or publish on SSSB. Multiple logistic regressions were performed to assess whether taxa studied, education level, or identification within the LGBTQ+ community predicted observing, collecting data on, or publishing on SSSB, but none of these variables were significant predictors. These results provide preliminary evidence that SSSB occurs more frequently than what is available in the published record and suggest that this may be due to a publishing bias against anecdotal evidence.

Queering food security research: A critical analysis of 2SLGBTQ+ People's experiences of food insecurity in Toronto during the COVID-19 pandemic.

INTRODUCTION: Household food insecurity (HFI), stress, isolation, and discrimination are major determinants of health that disproportionately affect 2SLGBTQ + people. The COVID-19 pandemic potentially exacerbated these inequities. This study investigates HFI rates among 2SLGBTQ + adults living in diverse household conditions during the pandemic and explores the idea that heteronormative conceptions of the "household" may affect measurement of HFI. METHODS: Cross-sectional survey responses were collected from 437 self-identified 2SLGBTQ + people from Toronto, Canada between March and July 2021. The survey measured HFI, sexual/gender identities, socio-demographic factors, household composition, and psycho-social stress/distress. Multinomial logistic regression was used to assess variation in odds of marginal, moderate, and severe HFI in relation to sexual/gender identities, household composition, psycho-social distress, and socio-demographic covariates. RESULTS: Forty-two percent of respondents reported some level of HFI, with severe HFI higher among respondents who were bisexual, transgender/gender diverse, and/or assigned-female-at-birth. Living alone was associated with decreased odds of reporting marginal HFI but increased odds of moderate or severe HFI compared to living with a partner, family, or roommates; living with children was associated with decreased odds of both marginal and severe HFI. One indicator of psycho-social distress (perceived discrimination) was associated with higher odds of all levels of HFI, while the other (isolation) was associated with decreased odds of marginal HFI. CONCLUSION: These findings highlight the high prevalence of HFI linked with discrimination among 2SLGBTQ + individuals during the pandemic. The complicated results regarding household composition and social isolation may suggest a need to revise definitions of the household when measuring, monitoring, and seeking to mitigate HFI in 2SLGBTQ + communities.

Sexual minority status is associated with earlier recalled age of menarche: Evidence from the 2005-2016 National Health and Nutrition Examination Survey.

INTRODUCTION: Menarcheal timing is associated with growth, development, health, wellbeing, and reproduction across the lifespan. Although sexual orientation is a known correlate of health and developmental inequities, relatively little evolutionarily framed research has investigated sexual orientation-based variation in maturational timing. To improve our understanding of menarcheal timing among sexual minority (SM) people, we use a biocultural-evolutionary life history lens that takes into account the stresses of minoritization to examine the relationship between sexual orientation and self-reported age at menarche in a sample of American adults. METHODS: Using the U.S. National Health and Nutrition Examination Survey (NHANES), a large, nationally representative dataset (n = 9757), we fit multiple logistic regression models and survival curves to evaluate associations between sexual orientation, indicators of somatic and material resources during adolescence (e.g., education, citizenship, upper arm length), and self-reported menarche. RESULTS: SM respondents were more likely to report earlier (by 4-5 months) ages of menarche (p < .001). Post-hoc tests revealed that these differences were driven by bisexual (p < .001) and same-sex experienced (p < .001) relative to heterosexual and lesbian/gay respondents. Earlier menarcheal timing among SM respondents persisted after adjusting for socio-demographic factors and proxies of developmental conditions. DISCUSSION: Our findings reveal that SM status is associated with earlier ages of menarche, an important social and reproductive milestone. We argue that uniting life history theory with the minority stress hypothesis better explains differences in menarcheal timing by sexual orientation than previous paradigms. Investigators should attend to sexual orientation-based variation in maturational timing using holistic, inclusive approaches.

Systemic sclerosis in Native Americans of the American Southwest.

OBJECTIVE: Many indigenous non-Caucasian populations, including Native Americans, have been reported to have higher rates, distinct clinical phenotypes, increased complications, and greater severity of systemic sclerosis (SSc). However, little is known of SSc specifically in Native Americans of the American Southwest. This study compared the clinical and serologic manifestations and outcomes of SSc in Native Americans and non-Native Americans (non-Natives) of this region. METHODS: This cross-sectional retrospective study included 137 SSc patients (109 [80%] were non-Native and 28 [20%] were Native Americans) followed over a mean of 11.5 ± 7.6 years. Participants were repetitively evaluated with medical history, physical examination, echocardiography, chest imaging, and serologic testing. Disease characteristics and outcomes were statistically compared between Native Americans and non-Native patients. RESULTS: The estimated prevalence of SSc in Native Americans was 40.0 cases/100 000 vs 17.1 cases/100 000 for non-Natives (odds ratio 2.34, 95% confidence interval [CI] 1.55-3.55, P < .001). The cohorts were similar in terms age, age of onset, limited vs diffuse cutaneous SSc, telangiectasias, gastroesophageal reflux disease, Raynaud phenomenon, serologies, interstitial lung disease, pulmonary arterial hypertension, scleroderma renal crisis, cancer prevalence, and overall mortality (all P > .05). However, for Native Americans, mortality specifically from fatal infections was 3.94-fold that of non-Natives (hazard ratio 6.88, 95% CI 1.37-34.64; P < .001). CONCLUSION: In Native Americans of the American Southwest, SSc is increased in prevalence but is phenotypically similar to SSc in non-Natives. However, mortality due specifically to infection is increased in Native Americans with SSc.

Systemic sclerosis manifestations and clinical outcomes in Hispanics/Latinos of the American Southwest.

Objective: Certain Hispanic/Latino (Hispanic) populations have been reported to have higher rates and severity of systemic sclerosis; however, little is known of systemic sclerosis in the American Southwest. This study compared manifestations of systemic sclerosis in Hispanics with non-Hispanics of New Mexico. Methods: This cross-sectional longitudinal study included 109 systemic sclerosis patients followed over a mean of 12.6 ± 8.9 years. Subjects were repetitively evaluated including physical examination, echocardiography, chest imaging, and serologic testing and observed for complications. Disease characteristics and long-term outcomes were statistically compared between self-identified Hispanic and non-Hispanic subjects. Results: A total of 73 (67%) systemic sclerosis subjects were Hispanic and 36 (33%) were non-Hispanic. The cohorts were similar in mean age, age of systemic sclerosis onset, limited versus diffuse cutaneous systemic sclerosis, telangiectases, gastroesophageal reflux disease, Raynaud's phenomenon, autoantibody profile, interstitial lung disease, pulmonary hypertension, scleroderma renal crisis, mortality, and comorbid malignancy (all p > 0.05). However, the standardized mortality ratio was increased in both cohorts relative to age-adjusted mortality: Hispanic: 2.08, confidence interval (1.94-2.24); non-Hispanic: 1.56, confidence interval (1.46-1.68). Furthermore, the standardized incidence ratio for malignancy was increased in both cohorts: Hispanic: 1.45, confidence interval (1.35-1.56); non-Hispanic: 1.24, confidence interval (1.16-1.34). The mean age of cancer diagnosis occurred at a significantly younger age in Hispanics (Hispanics: 53.1 ± 9.7 years; non-Hispanics 63.7 ± 7.9 years; 95% confidence interval: -19 ⩽ 10.6 ⩽ 2.2; p = 0.016). Conclusion: Systemic sclerosis phenotype, autoantibodies, complications, outcomes, malignancy rates, and mortality are generally similar between Hispanics and non-Hispanics with systemic sclerosis in the American Southwest. However, age-adjusted comorbid malignancy and mortality rates are significantly increased in both groups.

Sexual orientation-based disparities in food security among adults in the United States: results from the 2003-2016 NHANES.

BACKGROUND: Access to sufficient, safe, culturally appropriate, and nutritious food is essential for maintaining both physical and mental health. Despite a growing body of evidence suggesting that sexual minority (SM) people experience significant disparities in socioeconomic and material resource security, there remains a paucity of empirical studies examining the prevalence of food insecurity among SM people relative to their heterosexual peers. OBJECTIVES: To determine the prevalence of adult and household food insecurity across sexual orientation groups in the United States after adjusting for multiple covariates. METHODS: We combined 7 cycles of US NHANES, 2003-2016 (N = 21,300) to examine sexual orientation-based disparities in adult food security among lesbian/gay (n = 373), bisexual (n = 606), same-sex experienced (SSE, n = 693), other sexual minorities (OSMs, n = 88), and heterosexual (n = 19,540) people. Food (in)security was measured using the US Food Security Survey Module and categorized as secure, marginally insecure, moderately insecure, and severely insecure. RESULTS: Severe adult food insecurity was higher among bisexuals (17.16%; 95% CI: 14.36, 20.38), SSE (13.71%; 95% CI: 11.34, 16.48), OSMs (12.50%; 95% CI: 7.04, 21.24), and lesbians/gays (13.14%; 95% CI: 10.07, 16.97) compared with heterosexuals (8.23%; 95% CI: 7.85, 8.62). Multivariable multinomial logistic regression analysis adjusting for gender, race/ethnicity, age, citizenship, education, household size, income, cycle year, emergency food use, and Supplemental Nutrition Assistance Program participation showed that bisexuals, OSMs, SSE, and lesbians/gays were more likely to experience moderate to severe food insecurity compared with heterosexuals. CONCLUSIONS: SM people are significantly more likely to experience increased likelihood of food insecurity relative to their heterosexual peers.

Biocultural approaches to transgender and gender diverse experience and health: Integrating biomarkers and advancing gender/sex research.

Transgender and gender diverse (TGD) people are increasingly visible in U.S. communities and in national media. With this increased visibility, access to gender affirming healthcare is also on the rise, particularly for urban youth. Political backlash and entrenchment in a gender binary, however, continue to marginalize TGD people, increasing risk for health disparities. The 2016 National Institute of Health recognition of sexual and gender minority people as a health disparities population increases available funding for much-needed research. In this article, we speak to the need for a biocultural human biology of gender/sex diversity by delineating factors that influence physiological functioning, mental health, and physical health of TGD people. We propose that many of these factors can best be investigated with minimally invasively collected biomarker samples (MICBS) and discuss how to integrate MICBS into research inclusive of TGD people. Research use of MICBS among TGD people remains limited, and wider use could enable essential biological and health data to be collected from a population often excluded from research. We provide a broad overview of terminology and current literature, point to key research questions, and address potential challenges researchers might face when aiming to integrate MCIBS in research inclusive of transgender and gender diverse people. We argue that, when used effectively, MICBS can enhance human biologists' ability to empirically measure physiology and health-related outcomes and enable more accurate identification of pathways linking human experience, embodiment, and health.

Sexual orientation-based disparities in bone health: Evidence of reduced bone mineral density and mineral content among sexual minority men but not women in multiple NHANES waves.

INTRODUCTION: Sexual minority (SM) people experience significant stress associated with stigma, contributing to a higher rate of adverse health outcomes. Several known factors (eg, smoking) elevate risk of poor bone health, but to date little research has examined disparities in bone health among SM people. To address this, we analyzed sexual orientation differences in an available bone mineral density (BMD) cross-sectional dataset assessed via dual X-ray absorptiometry. METHODS: We combined the 2007 to 2008, 2009 to 2010, and 2013 to 2014 cycles of US National Health and Nutrition Examination Survey to examine sexual orientation-based differences in z-scored BMD in the proximal femur (greater trochanter and intertrochanter locations), bone mineral content (BMC) in the femur and spine, and osteoporosis risk among Lesbian/Gay (n = 53), Bisexual (n = 97), Same-Sex Experienced (n = 103), and Heterosexual (n = 2990) adults. RESULTS: Sexual orientation-based disparities in bone mass were observed across all anatomical sites. This effect was due to differences between heterosexual and gay men and persisted in linear regressions after adjusting for risk factors. We found differences in femoral and femoral neck BMC in heterosexual and gay men (P = .02) and in femoral, femoral neck and spinal BMC between heterosexual and bisexual women (P = .05). Sexual orientation remained significant in BMC regressions. CONCLUSION: Our findings suggest that SM men but not women are at greater risk for poor bone health relative to heterosexuals and this disparity is independent of the lifestyle and psychosocial risks included in our models.

Management of extracellular volume in patients with end-stage kidney disease and severe hyperglycemia.

This commentary addresses volume replacement in hyperglycemic crises in patients with end-stage kidney disease (ESKD). The management of volume issues in this group of patients should not be based on guidelines for management of hyperglycemic crises, but should be individualized and based on directed patient medical history, physical examination, and imaging of the heart and lungs. A scheme for combining information from these three sources is provided.

Dialysis-associated hyperglycemia: manifestations and treatment.

PURPOSE: Dialysis-associated hyperglycemia (DAH), is associated with a distinct fluid and electrolyte pathophysiology. The purpose of this report was to review the pathophysiology and provide treatment guidelines for DAH. METHODS: Review of published reports on DAH. Synthesis of guidelines based on these reports. RESULTS: The following fluid and solute abnormalities have been identified in DAH: (a) hypoglycemia: this is a frequent complication of insulin treatment and its prevention requires special attention. (b) Elevated serum tonicity. The degree of hypertonicity in DAH is lower than in similar levels of hyperglycemia in patients with preserved renal function. Typically, correction of hyperglycemia with insulin corrects the hypertonicity of DAH. (c) Extracellular volume abnormalities ranging from pulmonary edema associated with osmotic fluid shift from the intracellular into the extracellular compartment as a consequence of gain in extracellular solute (glucose) to hypovolemia from osmotic diuresis in patients with residual renal function or from fluid losses through extrarenal routes. Correction of DAH by insulin infusion reverses the osmotic fluid transfer between the intracellular and extracellular compartments and corrects the pulmonary edema, but can worsen the manifestations of hypovolemia, which require saline infusion. (d) A variety of acid-base disorders including ketoacidosis correctable with insulin infusion and no other interventions. (e) Hyperkalemia, which is frequent in DAH and is more severe when ketoacidosis is also present. Insulin infusion corrects the hyperkalemia. Extreme hyperkalemia at presentation or hypokalemia developing during insulin infusion require additional measures. CONCLUSIONS: In DAH, insulin infusion is the primary management strategy and corrects the fluid and electrolyte abnormalities. Patients treated for DAH should be monitored for the development of hypoglycemia or fluid and electrolyte abnormalities that may require additional treatments.

Atypical Chronic Inflammatory ANCA-Positive Deforming Arthritis After Cocaine-Levamisole Exposure.

BACKGROUND/OBJECTIVE: Immunostimulatory drugs including immune checkpoint inhibitors and levamisole can induce inflammatory disease including vasculitis, rashes, tissue necrosis, and arthritis. METHODS: This prospective cohort study determined the 5-year outcomes of cocaine-levamisole-induced inflammatory disease as to outcomes and survival. Thirty-one consecutive cocaine-levamisole autoimmune patients and 45 primary vasculitis patients were characterized as to clinical differentiating features, antineutrophil cytoplasmic antibody (ANCA) status, treatment, the presence of acute and chronic arthritis, and 5-year outcome. RESULTS: Seventy-one percent (22/31) of cocaine-levamisole vasculopathy cases were ANCA positive (86% p-ANCA and 14% c-ANCA), whereas 53% (23/45) of the primary vasculitis were ANCA positive (p = 0.04). The ANCA-positive cocaine-levamisole cohort at onset were characterized by younger age (45 ± 12 vs 53 ± 14 years, p = 0.04), superficial skin necrosis (82% vs 54%, p = 0.036), depressed complement C3 (27% vs 4%, p = 0.33), antiphospholipid antibodies (50% vs 4%, p < 0.001), neutropenia (18% vs 0%, p = 0.044), and elevated antimyeloperoxidase (MPO) antibody levels (100% vs 67%, p < 0.001). Chronic cocaine-levamisole disease was characterized by severe cicatrical deformities of the face and extremities (45.5% vs 8.3%, p = 0.005). Arthralgias (71% vs 82%, p = 0.19) and acute arthritis (33% vs 32%, p = 0.25) were similar between the 2 groups. However, a substantial proportion cocaine-levamisole-induced autoimmune patients (18% vs 0%, p = 0.045) developed a chronic deforming inflammatory arthritis that was rheumatoid factor, anti-cyclic-citrillinated antibody antibody, and HLA-B27 negative, but p-ANCA-and MPO antibody positive. CONCLUSIONS: Patients exposed to cocaine-levamisole may develop serious chronic sequelae including cicatrical cutaneous and facial deformities and an atypical seronegative, p-ANCA and MPO antibody-positive, HLA-B27-negative chronic deforming inflammatory arthritis.

Symptomatic Hyperglycemia in a Patient with Dialysis Ascites.

An anuric woman with ascites rapidly developed extreme hyperglycemia and seizures after hemodialysis. During development of hyperglycemia, the decrease in serum sodium concentration (Δ[Na]) was nearly twice the value predicted by a formula accounting for the degree of hyperglycemia and the intracellular-to-extracellular volume ratio. The prediction assumed that ascitic fluid is part of the extracellular volume. Potential contributors to the development of seizures include the rapid development of severe hypertonicity, a remote history of seizure disorder and development of dialysis disequilibrium syndrome. Observations in peritoneal dialysis suggest that fluid with sodium concentration lower than in the ascitic fluid is transferred from the abdominal cavity into the blood during rapid development of hyperglycemia. In this case, Δ[Na], which determines the tonicity level expected after correction of hyperglycemia, resulted from exit of both intracellular and ascitic fluid into the extracellular compartment and, therefore, ascitic fluid functions as an extension of the intracellular fluid.

Hyperglycemic Crisis in an Anuric Peritoneal Dialysis Patient with Profound and Symptomatic Hypertonicity.

An anuric peritoneal dialysis patient with diabetes mellitus, congestive heart failure, and anasarca developed severe hyperglycemia with hypertonicity causing profound neurological manifestations after prolonged and continuous use of hypertonic (4.25%) dextrose dialysate. She expired with hypotensive shock from a new myocardial infarction soon after completion of treatment with insulin infusion. The degree of the presenting hypertonicity far exceeded the value expected from the degree of hyperglycemia. We identified prolonged peritoneal dialysis with hypertonic solutions and profound extracellular volume expansion as the causes of the excessive hypertonicity. Hyperglycemia developing in diabetic patients treated for anasarca by peritoneal dialysis after continuous use of hypertonic dextrose dialysate is associated with the risk of excessive hypertonicity with severe clinical manifestations.

4-Methylmethcathinone (mephedrone): neuropharmacological effects of a designer stimulant of abuse.

The designer stimulant 4-methylmethcathinone (mephedrone) is among the most popular of the derivatives of the naturally occurring psychostimulant cathinone. Mephedrone has been readily available for legal purchase both online and in some stores and has been promoted by aggressive Web-based marketing. Its abuse in many countries, including the United States, is a serious public health concern. Owing largely to its recent emergence, there are no formal pharmacodynamic or pharmacokinetic studies of mephedrone. Accordingly, the purpose of this study was to evaluate effects of this agent in a rat model. Results revealed that, similar to methylenedioxymethamphetamine, methamphetamine, and methcathinone, repeated mephedrone injections (4× 10 or 25 mg/kg s.c. per injection, 2-h intervals, administered in a pattern used frequently to mimic psychostimulant "binge" treatment) cause a rapid decrease in striatal dopamine (DA) and hippocampal serotonin (5-hydroxytryptamine; 5HT) transporter function. Mephedrone also inhibited both synaptosomal DA and 5HT uptake. Like methylenedioxymethamphetamine, but unlike methamphetamine or methcathinone, repeated mephedrone administrations also caused persistent serotonergic, but not dopaminergic, deficits. However, mephedrone caused DA release from a striatal suspension approaching that of methamphetamine and was self-administered by rodents. A method was developed to assess mephedrone concentrations in rat brain and plasma, and mephedrone levels were determined 1 h after a binge treatment. These data demonstrate that mephedrone has a unique pharmacological profile with both abuse liability and neurotoxic potential.

Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration.

Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity.

Recruitment and derecruitment characteristics of motor units in a hand muscle of young and old adults.

The significant decline in motor neuron number after approximately 60 yr of age is accompanied by a remodeling of the neuromuscular system so that average motor unit force increases and the ability of old adults to produce an intended force declines. One possible explanation for the loss of movement precision is that the remodeling increases the difference in recruitment forces between successively recruited motor units in old adults and this augments force variability at motor unit recruitment. The purpose of the study was to compare the forces and discharge characteristics of motor units in a hand muscle of young and old adults at motor unit recruitment and derecruitment. The difference in recruitment force between pairs of motor units did not differ between young (n=54) and old adults (n=56; P=0.702). However, old adults had a greater proportion of contractions in which motor units discharged action potentials transiently before discharging continuously during the ramp increase in force (young: 0.32; old: 0.41; P=0.045). Force variability at motor unit recruitment was greater for old adults compared with young adults (Por=0.729). These results suggest that the difference in force between the recruitment of successive motor units does not differ between age groups, but that motor unit recruitment may be more transient and could contribute to the greater variability in force observed in old adults during graded ramp contractions.

Methamphetamine-induced dopaminergic deficits and refractoriness to subsequent treatment.

Repeated high-dose methamphetamine administrations can cause persistent dopaminergic deficits. As individuals abusing methamphetamine are often exposed to recurrent high-dose administration, the impact of its repeated exposure merits investigation. Accordingly, rats were pretreated with repeated high-dose injections of methamphetamine, and subsequently "challenged" with the same neurotoxic regimen 7 or 30 days later. Results revealed that the initial methamphetamine treatment caused persistent deficits in striatal dopamine levels, dopamine transporter function, and vesicular monoamine transporter-2 function. The subsequent methamphetamine challenge treatment was without further persistent effects on these parameters, as assessed 7 days after the challenge, regardless of the interval (7 or 30 days) between the initial and challenge drug exposures. Similarly, a methamphetamine challenge treatment administered 7 days after the initial drug treatment was without further acute effect on dopamine transporter or VMAT-2 function, as assessed 1 h later. Thus, this study describes a model of resistance, possibly explained by: 1) the existence of dopaminergic neurons that are a priori refractory to deficits caused by methamphetamine; 2) the existence of dopaminergic neurons made persistently resistant consequent to a neurotoxic methamphetamine exposure; and/or 3) altered activation of post-synaptic basal ganglia systems necessary for the elaboration of methamphetamine-induced dopamine neurotoxicity.

Mechanisms underlying methamphetamine-induced dopamine transporter complex formation.

Repeated, high-dose methamphetamine (METH) administrations cause persistent dopaminergic deficits in rodents, nonhuman primates, and humans. In rats, this treatment also causes the formation of high-molecular mass (greater than approximately 120 kDa) dopamine transporter (DAT)-associated complexes, the loss of DAT monomer immunoreactivity, and a decrease in DAT function, as assessed in striatal synaptosomes prepared 24 h after METH treatment. The present study extends these findings by demonstrating the regional selectivity of DAT complex formation and monomer loss because these changes in DAT immunoreactivity were not observed in the nucleus accumbens. Furthermore, DAT complex formation was not a consequence limited to METH treatment because it was also caused by intrastriatal administration of 6-hydroxydopamine. Pretreatment with the D2 receptor antagonist, eticlopride [S-(-)-3-chloro-5-ethyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-hydroxy-2-methoxybenzamide hydrochloride], but not the D1 receptor antagonist, SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride], attenuated METH-induced DAT complex formation. Eticlopride pretreatment also attenuated METH-induced DAT monomer loss and decreases in DAT function; however, the attenuation was much less pronounced than the effect on DAT complex formation. Finally, results also revealed a negative correlation between METH-induced DAT complex formation and DAT activity. Taken together, these data further elucidate the underlying mechanisms and the functional consequences of repeated administrations of METH on the DAT protein. Furthermore, these data suggest a multifaceted role for D2 receptors in mediating METH-induced alterations of the DAT and its function.