Primary conjunctival sporotrichosis in three cats from Northeastern Brazil.

INTRODUCTION: Classically, sporotrichosis occurs as a chronic granulomatous lymphocutaneous infection. The extracutaneous form is uncommon and may affect the eye without cutaneous involvement. The most frequent form of ocular sporotrichosis reported in humans is a granulomatous conjunctivitis. There are no previous reports on primary ocular sporotrichosis in cats. PROCEDURES: Three mixed breed cats rescued from shelters were referred by the veterinarian for ophthalmic evaluation with a complaint of conjunctivitis nonresponsive to treatment with no evidence of skin disease or systemic disease. Complete ophthalmic examination, conjunctival cytology, and microbiological analysis were performed. RESULTS: Ophthalmic examinations revealed epiphora, purulent ocular discharge, conjunctival hyperemia, and a mass in the palpebral conjunctiva. Conjunctival cytology revealed segmented and degenerated neutrophils, conjunctival epithelial cells, and an abundant number of round and oval cells compatible with Sporothrix spp. Microbiological culture was performed and confirmed the presence of fungi from the Sporothrix schenckii complex. All animals were treated with oral itraconazole; two animals received topical itraconazole in association with oral treatment. Case 1 was refractory to treatment, and iodate potassium was combined with itraconazole therapy without resolution at the time of this publication. Cases 2 and 3 had complete resolution of conjunctival lesions with four months of oral and topical itraconazole therapy. CONCLUSION: Conjunctival sporotrichosis should be considered as a differential diagnosis of conjunctivitis in cats from endemic regions. Conjunctival cytology is an important tool that can aid early diagnosis.

Polymorphisms of the genes CTLA4, PTPN22, CD40, and PPARG and their roles in Graves' disease: susceptibility and clinical features.

PURPOSE: CTLA4, PTPN22, and CD40 are immune-regulatory genes strongly associated with GD, as well as PPARG, but their clinical significance in different populations is still uncertain. METHODS: We genotyped 282 Brazilian GD patients (234 women and 48 men, 39.80 ± 11.69 years old), including 144 patients with GO, and 308 healthy control individuals (246 women and 62 men, 36.86 ± 12.95 years old). RESULTS: A multivariate analysis demonstrated that the inheritance of the GG genotype rs3087243 of CTLA4 (OR = 2.593; 95% CI = 1.630-4.123; p < 0.0001) and the CC genotype of rs3789607 of PTPN22 (OR = 2.668; 95% CI = 1.399-5.086; p = 0.0029) consisted in factors independent of the susceptibility to GD. The inheritance of polymorphic genotypes of rs5742909 of CTLA4 was associated with older age at the time of diagnosis (42.90 ± 10.83 versus 38.84 ± 11.81 years old; p = 0.0105), with higher TRAb levels (148.17 ± 188.90 U/L versus 112.14 ± 208.54 U/L; p = 0.0229) and the need for higher therapeutic doses of radioiodine (64.23 ± 17.16 versus 50.22 ± 16.86; p = 0.0237). The inheritance of the CC genotype of rs1883832 CD40 gene was more frequent among women (69.65%) than men (52.00%; p = 0.0186). The polymorphic genotype of PPARG gene (rs1801282) was associated with TPOAb positivity (p = 0.0391), and the GG genotype of rs2476601 of PTPN22 gene was associated with positivity for both TgAb (p = 0.0360) and TPOAb (p < 0.0001). Both polymorphic genotypes rs2476601 and rs3789607 of the PTPN22 gene were more frequent among nonsmoking patients (p = 0.0102 and p = 0.0124, respectively). CONCLUSIONS: Our data confirm the important role of CTLA4 polymorphisms in GD susceptibility; demonstrate the role of PTPN22 polymorphisms in patients' clinical features; and suggest these genes may influence the severity of the disease.

Neurotoxicity of low-level lead exposure: History, mechanisms of action, and behavioral effects in humans and preclinical models.

Lead is a neurotoxin that produces long-term, perhaps irreversible, effects on health and well-being. This article summarizes clinical and preclinical studies that have employed a variety of research techniques to examine the neurotoxic effects of low levels of lead exposure. A historical perspective is presented, followed by an overview of studies that examined behavioral and cognitive outcomes. In addition, a short summary of potential mechanisms of action is provided with a focus on calcium-dependent processes. The current level of concern, or reference level, set by the CDC is 5 µg/dL of lead in blood and a revision to 3.5 µg/dL has been suggested. However, levels of lead below 3 µg/dL have been shown to produce diminished cognitive function and maladaptive behavior in humans and animal models. Because much of the research has focused on higher concentrations of lead, work on low concentrations is needed to better understand the neurobehavioral effects and mechanisms of action of this neurotoxic metal.

Differences between adolescents and adults in the acute effects of PCP and ketamine and in sensitization following intermittent administration.

Adolescence is a phase of development during which many physiological and behavioral changes occur, including increased novelty seeking and risk taking. In humans, this is reflected in experimentation with drugs. Research demonstrates that drug use that begins during adolescence is more likely to lead to addiction than drug use that begins later in life. Despite this, relatively little is known of the effects of drugs in adolescence, and differences in response between adolescents and adults. PCP and ketamine are popular club drugs, both possessing rewarding properties that could lead to escalating use. Drug sensitization (or reverse tolerance), which refers to an increase in an effect of a drug following repeated use, has been linked with the development of drug cravings that is a hallmark of addiction. The current work investigated the acute response and the development of sensitization to PCP and ketamine in adolescent and adult rats. Periadolescent Sprague-Dawley rats (30days or 38days of age), and young adults (60days of age) received PCP (6mg/kg IP) or ketamine (20mg/kg IP) once every three days, for a total of five drug injections. Adolescents and adults showed a stimulant response to the first injection of either drug, however the response was considerably greater in the youngest adolescents and lowest in the adults. With repeated administration, adults showed a robust escalation in activity that was indicative of the development of sensitization. Adolescents showed a flatter trajectory, with similar high levels of activity following an acute treatment and after five drug treatments. The results demonstrate important distinctions between adolescents and adults in the acute and repeated effects of PCP and ketamine.

Regulação assistencial ambulatorial no Município do Rio de Janeiro, RJ: efeitos da inserção da APS na regulação / Ambulatory assistance regulation in Rio de Janeiro-RJ: effects of APS inserting in regulation

A regulação assistencial adequada melhora a equidade no acesso à atenção especializada conforme a necessidade das pessoas, tornando-se um instrumento para a garantia da atenção integral. A crescente regulamentação do SUS responsabilizou os municípios pela regulação assistencial para garantir a integralidade e o adequado funcionamento das redes de atenção à saúde. O município do Rio de Janeiro, após diferentes configurações, passou a regular as vagas de procedimentos especializado através da plataforma web SISREG, desenvolvida pelo DATASUS. Em junho de 2012, a gestão municipal descentralizou a regulação ambulatorial e empoderou os médicos responsáveis técnicos das unidades básicas de saúde para exercer tal função. O presente estudo objetivou analisar os efeitos da inserção dos profissionais da Atenção Primária à Saúde no processo de regulação assistencial ambulatorial no município do Rio de Janeiro, RJ na qualidade da regulação e nas filas de espera. Quatro procedimentos foram analisados, tomados como marcadores: consulta em oftalmologia geral-geral, consulta em cirurgia geral-geral, consulta em obstetrícia – alto risco geral e mamografia bilateral- rastreamento. A partir de dados do SISREG foram comparados número de vagas, status das solicitações, tempo médio de espera geral e de acordo com a classificação de risco dos quatro procedimentos, entre janeiro de 2011 e dezembro de 2013...

An adequate healthcare regulation improves the equity to the access to the specialized care according to the person needs, and became a tool to assure an access to a comprehensive health care. The increasing regulation of the Brazilian Unified Health System (hereby SUS) passed the responsibility to the municipalities for the healthcare regulation to assure the comprehensiveness and the adequate operation of the healthcare network. Rio de Janeiro city, after several configuration attempts, began to regulate the specialized procedures through the web SISREG platform, developed by DATASUS. In June 2012, the municipal management decentralized the outpatient regulation and empowered doctors that were technical managers of the basic health care units to serve as refugators. (...) The quality of the regulation presented improvement for the four precedures, with the increase in the returned and denied requisitions, showing a more careful evaluation from the managers. From the data analysis, based on the literature, it can be concluded that the set of measurements taken by the Rio Janeiros SMS incurred in the reduction of the average waiting time, and that increase of the number of schedule is one of the most effective measurement. It is necessary to search for new perspectives for the accountability of APS and the oncoming of the providers of several levels to coordinate the care in a way the healthcare regulation became a tool for the improvement in the equity and not another barrier to the access of the users...

Case for diagnosis.

An 80-year-old Caucasian male patient was referred for evaluation of a rapidly growing, asymptomatic, erythematous nodule measuring 2 cm in diameter on his left cheek. The lesion had been present for four months. Dermoscopy revealed a homogeneous pink background with polymorphous telangiectatic vessels. Histopathology showed tumors in the deep dermis and subcutis composed of round cells with scant cytoplasm. Immunohistochemical staining was positive for CK20 confirming the diagnosis of Merkel cell carcinoma.

Case for diagnosis / Caso para diagnóstico

An 80-year-old Caucasian male patient was referred for evaluation of a rapidly growing, asymptomatic, erythematous nodule measuring 2 cm in diameter on his left cheek. The lesion had been present for four months. Dermoscopy revealed a homogeneous pink background with polymorphous telangiectatic vessels. Histopathology showed tumors in the deep dermis and subcutis composed of round cells with scant cytoplasm. Immunohistochemical staining was positive for CK20 confirming the diagnosis of Merkel cell carcinoma.

Paciente de 80 anos, branco, sexo masculino, encaminhado para avaliação de nódulo eritematoso de 2 cm, assintomático, de crescimento rápido, localizado na região malar esquerda, com quatro meses de evolução. À dermatoscopia visualizou-se fundo homogêneo róseo com telangiectasias polimorfas. O exame anatomopatológico revelou massas tumorais atingindo a derme profunda e o subcutâneo, compostas por células arredondadas, de citoplasma escasso. A imunohistoquímica foi positiva para CK20, confirmando o diagnóstico de carcinoma de células de Merkel.

Role of the prefrontal cortex and nucleus accumbens in reinstating methamphetamine seeking.

Although the involvement of the medial prefrontal cortex projection to the nucleus accumbens in the reinstatement of cocaine seeking has been well studied, it is not known if this projection plays a similar role in the reinstatement of cue- and methamphetamine-induced drug seeking in animals extinguished from methamphetamine self-administration. Accordingly, following extinction from long-access methamphetamine self-administration, rats were bilaterally microinjected with either a combination of the GABA agonists baclofen/muscimol or vehicle (artificial cerebrospinal fluid) into the infralimbic or prelimbic subcompartments of the medial prefrontal cortex or into the shell or core subcompartments of the nucleus accumbens. Similar to cocaine seeking, inactivation of either the prelimbic cortex or accumbens core eliminated cue- and methamphetamine-induced reinstatement, and inactivation of neither the infralimbic cortex nor shell subcompartments inhibited methamphetamine-induced drug seeking. However, in contrast to previous reports with cocaine, cue-induced reinstatement of methamphetamine seeking was inhibited by inactivation of the infralimbic cortex. In conclusion, although a primary role in reinstated drug seeking by the prelimbic and the accumbens core is similar between cocaine and methamphetamine, the recruitment of the infralimbic cortex by conditioned cues differs between these two psychostimulant drugs.

Extended methamphetamine self-administration in rats results in a selective reduction of dopamine transporter levels in the prefrontal cortex and dorsal striatum not accompanied by marked monoaminergic depletion.

Chronic abuse of methamphetamine leads to cognitive dysfunction and high rates of relapse, paralleled by significant changes of brain dopamine and serotonin neurotransmission. Previously, we found that rats with extended access to methamphetamine self-administration displayed enhanced methamphetamine-primed reinstatement of drug-seeking and cognitive deficits relative to limited access animals. The present study investigated whether extended access to methamphetamine self-administration produced abnormalities in dopamine and serotonin systems in rat forebrain. Rats self-administered methamphetamine (0.02-mg/i.v. infusion) during daily 1-h sessions for 7 to 10 days, followed by either short- (1-h) or long-access (6-h) self-administration for 12 to 14 days. Lever responding was extinguished for 2 weeks before either reinstatement testing or rapid decapitation and tissue dissection. Tissue levels of monoamine transporters and markers of methamphetamine-induced toxicity were analyzed in several forebrain areas. Long-access methamphetamine self-administration resulted in escalation of daily drug intake ( approximately 7 mg/kg/day) and enhanced drug-primed reinstatement compared with the short-access group. Furthermore, long-, but not short-access to self-administered methamphetamine resulted in persistent decreases in dopamine transporter (DAT) protein levels in the prefrontal cortex and dorsal striatum. In contrast, only minor alterations in the tissue levels of dopamine or its metabolites were found, and no changes in markers specific for dopamine terminals or glial cell activation were detected. Our findings suggest that persistent methamphetamine seeking is associated with region-selective changes in DAT levels without accompanying monoaminergic neurotoxicity. Greater understanding of the neuroadaptations underlying persistent methamphetamine seeking and cognitive deficits could yield targets suitable for future therapeutic interventions.

Developmental lead exposure attenuates methamphetamine dose-effect self-administration performance and progressive ratio responding in the male rat.

Perinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy of various psychoactive drugs (e.g., cocaine, opiates) across the phases of initial selection, use, and abuse [Nation J.R., Cardon A.L., Heard H.M., Valles R., Bratton G.R. Perinatal lead exposure and relapse to drug-seeking behavior in the rat: a cocaine reinstatement study. Psychopharmacol 2003;168: 236-243.; Nation J.R., Smith K.R., Bratton G.R. Early developmental lead exposure increases sensitivity to cocaine in a self-administration paradigm. Pharmacol Biochem Behave 2004; 77: 127-13; Rocha A., Valles R., Cardon A.L., Bratton G.R., Nation J.R. Enhanced acquisition of cocaine self-administration in rats developmentally exposed to lead. Neuropsychopharmacol 2005; 30: 2058-2064.]. However, changes in sensitivity to methamphetamine across the phases of drug abuse have not been examined in animals perinatally exposed to lead. Because the mainstream popularity of methamphetamine in the United States is increasing and lead exposure continues to be widespread, an examination of this drug and how it may be modified by perinatal exposure to lead is warranted. The studies reported here examined the effects of perinatal lead exposure on adult self-administration of intravenous (i.v.) methamphetamine across the maintenance phase of drug addiction. Experiment 1 examined dose-effect patterns in control and lead-exposed animals. Experiment 2 evaluated control and lead-exposed animals in a progressive ratio task. Female rats were administered a 16-mg lead or a control solution for 30 days prior to breeding with non-exposed males. Exposure continued through pregnancy and lactation and was discontinued at weaning (postnatal day [PND] 21). Animals born to control or lead-exposed dams received indwelling jugular catheters as adults (PND 70) and subsequently were randomly assigned to one of the two studies, using only one male rat per litter for each study. The data showed a general attenuation of the reinforcement efficacy of methamphetamine in animals perinatally exposed to lead, as compared to control animals.

Developmental lead exposure alters methamphetamine self-administration in the male rat: acquisition and reinstatement.

The rate of acquisition of drug self-administration and the return to drug seeking are important elements of the overall drug profile, and are essential factors in understanding risks associated with drug abuse. Experiment 1 examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous (i.v.) methamphetamine self-administration. Experiment 2 investigated the effects of perinatal lead exposure on drug-maintained responding in a reinstatement (relapse) paradigm. In Experiment 1, female rats were gavaged daily with 0 or 16 mg lead for 30 days prior to breeding with nonexposed males. Lead exposure continued through gestation and lactation and was discontinued at weaning (postnatal day [PND] 21). Male rats born to control or lead-exposed dams were tested daily as adults in an acquisition paradigm that incorporated both Pavlovian and operant components. An initial 3-h autoshaping period preceded a 3-h self-administration period. For 35 daily training sessions i.v. methamphetamine infusions [inf] (0.02 mg/kg) were paired with the extension and retraction of a lever (autoshaping), while inf occurred during self-administration only when a lever press was executed (FR-1). In Experiment 2 animals developmentally exposed to lead were trained on an FR-2 to self-administer methamphetamine (0.04 mg/kg/inf) and then placed on an extinction schedule prior to receiving intraperitoneal (i.p.) priming injections of saline, 0.50, 1.00, or 1.50 mg/kg methamphetamine. The findings from Experiment 1 showed that acquisition was delayed in rats born to lead-exposed dams gavaged daily with 16 mg lead throughout gestation and lactation when a 0.02-mg/kg/inf of methamphetamine served as the reinforcement outcome. Additional data from Experiment 2 indicated priming cues (injections of methamphetamine [i.p.]) administered after extinction were less likely to occasion a return to drug seeking (relapse) in the 16-mg group relative to the 0-mg control group. These results suggest perinatal lead exposure alters patterns of methamphetamine self-administration during the adult cycle.

The effects of concurrent administration of +/-3,4-methylenedioxymethamphetamine and cocaine on conditioned place preference in the adult male rat.

Conditioned place preference (CPP), a commonly used model for studying the role of contextual cues in drug reward and drug seeking, was employed to explore possible behavioral interactions between (+/-)3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") and cocaine. On each of four occasions, adult male rats received one of three doses of MDMA (0 mg/kg, 5 mg/kg, 10 mg/kg; administered subcutaneously [s.c.]) combined with one of three doses of cocaine (0 mg/kg, 2.5 mg/kg, 5 mg/kg; administered intraperitoneally [i.p.]), and were then tested in a CPP paradigm. The results showed MDMA-induced CPP at a unit dose of 5 mg/kg, but at the 10 mg/kg dose there was a return to baseline (control) performance levels. For cocaine alone, CPP increased in a linear fashion as the drug dose was increased. Concurrent administration resulted in antagonism of each drug, but there was evidence that this pattern was reversible at higher doses of the respective drugs. These data are instructive insofar as they suggest that the behavioral and neurochemical effects of MDMA and cocaine presented in isolation are dramatically altered when the two drugs are presented in combination.

Análisis de eficiencia técnica de la red pública de presentadores de servicios dentro del Sistema General de Seguridad Social en Salud / Analysis of technical efficiency of the public network of presenters of services within the General System of Social Security in Health

La evaluación de eficiencia para los hospitales públicos a nivel nacional se hace bajo la premisa de que la unidad hospitalaria es parte del sistema general de salud y en particular de la red de atención. La eficiencia se mide desde dos perspectivas, la primera la dada por los indicadores de recursos, aprovechamiento, funcionamiento y calidad; y la segunda perspectiva es la dada por un modelo de frontera estocástica. Los resultados indican que los hospitales públicos de segundo y tercer nivel, así como los centros de salud, son eficientes técnicamente, mientras que en los hospitales de primer nivel se evidencia un comportamiento ineficiente desde el punto de vista técnico, y la evidencia indica que esta ineficiencia es un problema de las unidades en el sistema, donde el componente del sistema refiere a una inadecuada asignación de recursos.

The evaluation of the efficiency of public hospitals at national level is done under the assumption that the country has a general health system, and the hospitals belongs to this system, especiallybelongs to safety public health net. The efficiency is measure in two paths, the first given by the indicators of use, resources, functioning and quality. The second way is given by the adjustmentof the stochastic frontier. The results show that the public hospitals in second and third level, and primary health attention centers are efficient technically, while the evidence say that the first level public hospitals are inefficient like units, in the sense of technical use of the raw materials - technically inefficient -, and the exploratory analysis show that inefficient occurs because there are anot optimum assignation of resources, and according to the law this assignation is not a function of the hospital, it is a function of the system.

The effects of acquisition training schedule on extinction and reinstatement of cocaine self-administration in male rats.

Partial reinforcement is known to increase resistance to extinction (Rn) relative to training with continuous reinforcement. This phenomenon, referred to as the partial reinforcement extinction effect, is one of the most robust in learning and conditioning studies. Experiment 1 investigated manipulations known to affect the partial reinforcement extinction effect and determined their possible relevance for drug use patterns. Male rats received intravenous cocaine self-administration training under partial reinforcement (FR-10) training or continuous reinforcement (FR-1) conditions with either a low (0.25 mg/kg infusion) or a high cocaine dose (1.00 mg/kg infusion). Animals were placed on an extinction (recurrent nonreward) schedule for 10 days (1-hr sessions) prior to being tested for cue-induced reinstatement (single 2-hr session). Experiment 2 involved acquisition of cocaine self-administration under FR-1 conditions of short training (15 days) or extended training (30 days) with a low dose (0.25 mg/kg infusion) or a medium dose (0.50 mg/kg infusion) of cocaine reward prior to extinction or reinstatement. Experiment 1 showed that rats trained with FR-10-high dose outcomes exhibited greater Rn than the remaining groups. Additionally, FR-10-high dose and FR-10-low dose rats were more likely to return to active drug seeking during the reinstatement test. In Experiment 2, rats trained under FR-1-medium dose conditions were more persistent during extinction following short acquisition training than comparable rats experiencing extended acquisition training. The reinstatement test was conducted following extinction, in which it was observed that overtraining under FR-1-medium dose reward schedules resulted in a decrease in the tendency to return to active drug seeking.

The effects of the GABAA antagonist bicuculline on cocaine self-administration in rats exposed to lead during gestation/lactation.

The present investigation examined the effects of perinatal lead exposure on cocaine self-administration following a GABAA antagonist pretreatment. Female rats were exposed to either 0 or 16 mg lead daily for 30 days prior to breeding with unexposed males. Beginning on postnatal day (PND) 75, control (N=10) and lead-exposed (N=8) animals were trained to self-administer 0.50 mg/kg cocaine intravenously (IV). After stable responding was established, animals were tested at 0.03 and 0.06 mg/kg cocaine delivered intravenously (IV), combined with intraperitoneal (IP) administration of either saline, 0.50, 1.00 or 2.00 mg/kg bicuculline (a GABAA antagonist). The results showed that control animals increased self-administration responding at a cocaine dose of 0.06 mg/kg as bicuculline dose increased. Lead-exposed animals exhibited an opposite pattern, i.e., a decrease in active (cocaine) lever responding occurred as the bicuculline dose was increased. Results at the 0.03 mg/kg cocaine dose failed to show group separation, or significant changes consequent to the bicuculline pretreatment. The data suggest that GABA antagonism results in increased reward potency of a low dose of cocaine and further, that this effect is differentially expressed in animals exposed to perinatal lead.

Enhanced acquisition of cocaine self-administration in rats developmentally exposed to lead.

The rate of acquisition of drug self-administration may serve as a predictor of later drug-taking behavior, possibly influencing the vulnerability to use drugs. The present study examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous cocaine self-administration using an automated procedure that included both Pavlovian and operant components. For Experiment 1, female rats were gavaged daily with 0 or 16 mg lead for 30 days prior to breeding with nonexposed males. Metal administration continued through pregnancy and lactation and was discontinued at weaning (postnatal day (PND) 21). Animals born to control or lead-exposed dams subsequently were tested daily as adults in a preparation where sessions included an initial 3-h autoshaping period followed by a 3-h self-administration period where 0.20 mg/kg cocaine was delivered contingently. During autoshaping, intravenous cocaine infusions were paired with the extension and retraction of a lever, while infusions occurred during self-administration only when a lever press was executed (FR-1). The criterion for acquisition was a 2-day period during which a mean of 50 infusions/session occurred during self-administration. Animals were given 35 days to reach criterion. In Experiment 1, accelerated rates of acquisition of cocaine self-administration were evident for lead-exposed animals relative to controls. Overall, the number of self-administered cocaine infusions per session was significantly higher for lead-exposed rats as compared to control rats. Experiment 2 replicated Experiment 1 except that a higher dose of cocaine (0.80 mg/kg) was employed as the reinforcer, and 30 infusions/session was the set criterion. At the higher cocaine dose (Experiment 2), acquisition rates for control and lead-exposed animals were not markedly different, and significantly different infusion rates were not observed.

Exposure to cadmium during gestation and lactation decreases cocaine self-administration in rats.

This investigation examined the effects of perinatal cadmium exposure on subsequent self-administration of cocaine during the adult cycle. Female Sprague-Dawley rats were gavaged daily with 0.0 (14% sucrose solution, w/v) or 5.0 mg cadmium chloride (dissolved in 14% sucrose solution, w/v) for 30 days prior to breeding with non-exposed males. Dams continued to experience cadmium exposure through gestation and until pups were weaned at postnatal day (PND) 21. On PND 70, offspring were anesthetized and chronic indwelling jugular catheters were implanted. Following recovery, test subjects were trained in operant chambers to self-administer 0.500 mg/kg infusion (inf) intravenous cocaine on a fixed-ratio (FR) 2 schedule of reinforcement. Following acquisition, self-administration rates were tested for saline, 0.030, 0.060, 0.125, 0.250, and 0.500 mg/kg inf cocaine. Rats exposed developmentally to cadmium self-administered significantly less than controls at saline, 0.030, and 0.060 mg/kg inf cocaine. These data indicate that early-life cadmium exposure, a common exposure vector of which is the use of tobacco products, may affect cocaine sensitivity.

Self-administration of heroin in rats: effects of low-level lead exposure during gestation and lactation.

RATIONALE: Developmental lead exposure has been found to produce differential patterns of drug self-administration in adult animals. OBJECTIVES: The present study examined the effects of perinatal (gestation/lactation) lead exposure on adult patterns of heroin self-administration. METHODS: Female rats were gavaged daily with 0 mg or 16 mg lead for 30 days prior to breeding with non-exposed males. Metal administration continued through pregnancy and lactation and was discontinued at weaning [postnatal day 21 (PND 21)]. Animals born to control or lead-exposed dams received indwelling jugular catheters as adults and were randomly assigned to one of two studies. In experiment 1, animals were tested on a FR-2 schedule in an effort to examine differential sensitivity to heroin in an intravenous self-administration paradigm. Seven doses of heroin were selected ranging from 0.56 microg/kg to 36 microg/kg per infusion. In experiment 2, littermates were tested on a progressive ratio (PR) schedule in order to more explicitly determine the nature of the change in sensitivity to the drug. RESULTS: In experiment 1, lead-exposed animals responded for heroin at significantly lower rates across most doses as evidenced by a downward shift in the inverted-U dose-effect curve. Congruent with these findings, lead-exposed animals in experiment 2 exhibited a decrease in progressive ratio responding (lower breaking points) across all heroin doses, further suggesting that perinatal lead exposure attenuates opiate self-administration in adult animals by altering the rewarding efficacy of the drug. In experiment 2, it was determined further that lead-exposed animals had lower latencies to make the initial lever press for heroin. CONCLUSIONS: These results support previous literature suggesting that perinatal exposure to inorganic lead attenuates the effectiveness of opiates as a reinforcer when animals are tested in the adult life cycle.