Hypoalbuminemia in COVID-19: assessing the hypothesis for underlying pulmonary capillary leakage.

BACKGROUND: Since the first observations of patients with COVID-19, significant hypoalbuminaemia was detected. Its causes have not been investigated yet. OBJECTIVE: We hypothesized that pulmonary capillary leakage affects the severity of respiratory failure, causing a shift of fluids and proteins through the epithelial-endothelial barrier. METHODS: One hundred seventy-four COVID-19 patients with respiratory symptoms, 92 admitted to the intermediate medicine ward (IMW) and 82 to the intensive care unit (ICU) at Luigi Sacco Hospital in Milan, were studied. RESULTS: Baseline characteristics at admission were considered. Proteins, interleukin 8 (IL-8) and interleukin 10 (IL-10) in bronchoalveolar lavage fluid (BALF) were analysed in 26 ICU patients. In addition, ten autopsy ultrastructural lung studies were performed in patients with COVID-19 and compared with postmortem findings in a control group (bacterial pneumonia-ARDS and H1N1-ARDS). ICU patients had lower serum albumin than IMW patients [20 (18-23) vs 28 (24-33) g L-1 , P < 0.001]. Serum albumin was lower in more compromised groups (lower PaO2 -to-FiO2 ratio and worst chest X-ray findings) and was associated with 30 days of probability of survival. Protein concentration was correlated with IL-8 and IL-10 levels in BALF. Electron microscopy examinations of eight out of ten COVID-19 lung tissues showed loosening of junctional complexes, quantitatively more pronounced than in controls, and direct viral infection of type 2 pneumocytes and endothelial cells. CONCLUSION: Hypoalbuminaemia may serve as severity marker of epithelial-endothelial damage in patients with COVID-19. There are clues that pulmonary capillary leak syndrome plays a key role in the pathogenesis of COVID-19 and might be a potential therapeutic target.

Association between motor proficiency and oral health in people with intellectual disabilities.

BACKGROUND: People with intellectual disabilities (IDs) may be at increased risk of developing periodontal diseases and dental caries due to poor oral hygiene. Our aim was to investigate motor proficiency factors associated with presence of visible plaque and gingival bleeding in people with IDs. We were particularly interested in the level of dependence, manual coordination and fine manual control of people with ID, as well as the level of exhaustion of the primary caregiver. METHODS: In this cross-sectional study, 299 people with ID were evaluated for oral hygiene using the simplified Visible Plaque Index and for gum inflammation using the Gingival Bleeding Index. The Bruininks-Oseretsky Motor Proficiency Test assessed motor proficiency through fine manual control (fine motor integration and fine motor precision) and manual coordination (manual dexterity and upper limb coordination). The level of dependence was assessed by the Katz dependency index, and the caregiver was tested for exhaustion using the fatigue severity scale. Prevalence ratios [and 95% confidence intervals (CI)] were calculated using crude and adjusted Poisson regression with robust variance. RESULTS: The exhaustion of the caregiver was associated positively to visible plaque [prevalence ratio (PR) = 1.36; 95% CI 1.06-1.65]. For gingival bleeding, people with IDs that had better fine motor integration (PR = 0.49; 95% CI 0.33-0.75) and precision (PR = 0.50; 95% CI 0.26-0.94), as well as manual dexterity (PR = 0.62, 95% CI 0.49-0.77), presented better results. CONCLUSION: Poor oral hygiene and gum inflammation were associated with motor proficiency of people with IDs and caregivers' exhaustion. Interventions to improve the oral health of people with IDs should take into account such conditions.

Association between oropharyngeal dysphagia, oral functionality, and oral sensorimotor alteration.

OBJECTIVE: To evaluate whether the oral functionality and the oral sensorimotor alterations are associated with oropharyngeal dysphagia in community-dwelling older persons and long-term care older residents. METHODS: An exploratory study with 265 independent older persons of the southern state of Brazil. The diagnosis of dysphagia, as well as the condition of the oral sensorimotor system, was assessed by a speech-language therapist and the oral health status by a dentist. Poisson Regression with robust variance was used to calculate the crude and adjusted Prevalence Ratios (PR) and their respective confidence intervals of 95%. RESULTS: The mean age was 73.5 (±8.9) years, women represented 59.2% of the sample. The frequency of dysphagia in the studied population was 45.3% (n = 120), being more frequent in the long-term care older residents (62.5%; n = 75) than in the community-dwelling older persons (37.5%; n = 45). Individuals with four or more oral sensorimotor alterations (PR = 2.01; 95% CI 1.27-3.18), as well as those who presented a non-functional oral status (PR = 1.61; 95% CI 1.02-2.54) presented a higher frequency of dysphagia. Subgroup analysis indicates the same trend of results, when stratified by community-dwelling older persons and long-term older residents. CONCLUSION: A non-functional oral health status and oral sensorimotor alterations are associated with a higher prevalence of oropharyngeal dysphagia.

Toxoplasmosis in ring-tailed lemurs (Lemur catta) and a peahen (Pavo cristatus) in a zoological collection caused by the common toxoplasma genotype in wild animals in the US.

Toxoplasmosis is caused by the ubiquitous Apicomplexan protozoan Toxoplasma gondii. This pathogen affects domestic and wildlife species, but prosimians including ring-tailed lemurs (Lemur catta) are highly susceptible to infection with high mortality rates. Avian species are considered resistant to infection and are often used in surveillance efforts to determine genotypes of T. gondii present in geographical areas. This study describes the gross and histologic lesions of an outbreak of toxoplasmosis in a university-run zoological collection involving three ring-tailed lemurs and a peahen (Pavo cristatus). DNA was extracted from the liver of the lemurs and peahen to determine the genotype of T. gondii by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), which revealed that all samples were ToxoDB PCR-RFLP genotype #5 (haplogroup 12) that is common in wildlife in North America.

Immunohistochemical study of rabies virus within the central nervous system of domestic and wildlife species.

Immunohistochemistry using a commercial polyclonal antibody for lyssavirus was applied to 39 archival cases of rabies. Paraffin blocks from 13 different species were available, including 3 dogs, 4 cats, 1 pig, 6 cattle, 4 horses, 1 llama, 7 skunks (Mephitis mephitis), 7 raccoons (Procyon lotor), 1 bat (Myotis species), 1 white-tailed deer (Odocoileus virginianus), 1 bobcat (Lynx rufus), 2 gray foxes (Urocyon cinereoargenteus), and 1 red fox (Vulpes vulpes). All cases had previously been diagnosed as rabies using histopathology and/or fluorescent antibody testing. The immunohistochemistry technique successfully detected lyssavirus antigen in all cases. In species for which 3 or more samples were available, distributional trends were seen in 4 main brain regions: brainstem, cerebellum, hippocampus, and cerebrum. The best site for rabies virus detection in dogs and cats was the hippocampus. For cattle, viral antigen was most prominent in the brainstem, followed by the cerebellum. In horses, the cervical spinal cord and adjacent brainstem were the optimal sites for detecting rabies virus antigen. In raccoons and skunks, positive labeling was widely dispersed, so selection might be less important for these wildlife reservoir species. Immunohistochemistry should prove useful in enhancing the accuracy of rabies diagnosis through informed selection of brain sampling sites when composite sampling is not feasible. This immunohistochemical technique could provide reliable virus detection in formalin-fixed tissues in any potentially infected species.

Retrospective Analysis of Aetiological Agents Associated with Pulmonary Mycosis Secondary to Enteric Salmonellosis in Six Horses by Panfungal Polymerase Chain Reaction.

Pulmonary mycosis secondary to enterocolitis is an uncommon diagnosis in equine medicine, but is thought to result from mucosal compromise and translocation of enteric fungi. The aetiological agent associated with translocation is often identified based on fungal culture or hyphal features in histological sections. In order to understand better the aetiological agents involved, six horses diagnosed with Salmonella enteritis and concurrent pulmonary mycosis were identified retrospectively through a database search of veterinary teaching hospital records. Samples from these cases were subjected to polymerase chain reaction and sequencing of the internal transcribed spacer 2 (ITS-2) located between the 5.8S and 28S rRNA genes to identify the aetiological agent involved. Sequencing identified Aspergillus fumigatus, Aspergillus flavus, Fusarium spp., Cladosporium spp. and Curvularia spp. A single case had a dual infection with Fusarium spp. and A. fumigatus.

Cardiac Lesions of Natural and Experimental Infection by Parrot Bornaviruses.

Lymphoplasmacytic inflammation associated with bornavirus N protein occurs in the epicardial ganglia, myocardium and endocardium of birds diagnosed with proventricular dilatation disease (PDD). These pathological findings suggest that sudden death in psittacine birds might stem from cardiac compromise due to parrot bornavirus (PaBV) infection. Therefore, we investigated cardiac lesions in cases of PDD, searching databases from 1988 to 2019, and reviewed three experimental studies of PaBV infection. Fifty cases of PDD in birds infected naturally with PaBV and 27 cases of PDD in birds infected experimentally with PaBV (all having descriptions of inflammatory cardiac lesions) were reviewed. For each case, five regions of the heart were evaluated by light microscopy and immunohistochemistry (IHC). These regions were the epicardial ganglia/nerves, the endocardium, the myocardium, the Purkinje fibres and the great vessels. Sudden death was documented in 17/50 naturally infected cases, while 23/50 had digestive signs, and only 12/50 had neurological signs. Grossly, only five naturally-infected and five experimentally-infected cases had cardiomegaly or hydropericardium. Epicardial ganglioneuritis was the most consistent microscopical finding in natural (46/50) and experimental cases (26/27), followed by myocarditis (34/50) for naturally-infected and endocarditis for experimentally-infected birds (6/27). PaBV-2 antigen was detected most frequently by IHC in the epicardial ganglia (54/77) compared with the other tissues. This retrospective study demonstrates the presence of PaBV protein and inflammation in the heart of birds infected with PaBV and suggests a link between PaBV and cardiac disease and sudden death in psittacine birds.

Ovarian Teratocarcinoma in an Emu (Dromaius novaehollandiae): Histopathological and Immunohistochemical Characterization.

A 17-year-old female emu (Dromaius novaehollandiae) was presented for clinical evaluation due to a 3-week history of anorexia and progressive weight loss. The emu died after sedation. At necropsy examination, the ovary and the majority of the oviduct were effaced by a multinodular cystic mass and accompanied by 6 l of coelomic effusion. Histopathology revealed a neoplasm composed of well-differentiated, poorly organized tissues derived from ectoderm, mesoderm and endoderm. Tissues within the neoplasm expressed glial fibrillary acidic protein, desmin and cytokeratins AE1/AE3, respectively, confirming the diagnosis of teratocarcinoma.

Porcine respiratory disease complex after the introduction of H1N1/2009 influenza virus in Brazil.

From 2009 to 2015, 74 lungs from suckling (6.8%), nursing (70.3%), fattening (20.3%) pigs and pregnant sows (2.7%) with respiratory signs from pig farms in Southern Brazil were submitted to a diagnostic laboratory for necropsy and/or histologic examination and screening for respiratory agents by RT-qPCR, immunohistochemistry (IHC), virus isolation (VI) and subtyping for influenza A virus (IAV), IHC and nested PCR for Mycoplasma hyopneumoniae (Mhyo), PCR for porcine circovirus 2 (PCV2), RT-qPCR for porcine reproductive and respiratory syndrome virus (PRRSV) and bacterial culture. All lung samples were positive for IAV using RT-qPCR. Seventy-two lungs had histologic lesions associated with acute to subacute IAV infection characterized by necrotizing bronchiolitis/bronchitis or bronchointerstitial pneumonia with lymphocytic peribronchiolitis and bronchiolar/bronchial hyperplasia, respectively. Forty-nine lungs (66.2%) were positive by IHC for IAV nucleoprotein. The H1N1/2009 was the most common subtype and the only IAV detected in 58.1% of lungs, followed by H1N2 (9.5%) and H3N2 (6.8%). Coinfection of IAV and Mhyo was seen in 23 (31%) cases. Although 14.9% of the lungs were positive for PCV2 using PCR, no suggestive lesions of PCV2 disease were observed. Porcine reproductive and respiratory syndrome virus (PRRSV) was not detected, consistent with the PRRS-free status of Brazil. Secondary bacterial infections (8/38) were associated with suppurative bronchopneumonia and/or pleuritis. Primary IAV infection with Mhyo coinfection was the most common agents found in porcine respiratory disease complex (PRDC) in pigs in Southern Brazil.

Surgical Pleth Index guided analgesia blunts the intraoperative sympathetic response to laparoscopic cholecystectomy.

BACKGROUND: Surgical noxious stimuli generate a stress response with an increased sympathetic activity, potentially affecting the perioperative outcome. Surgical Pleth Index (SPI), derived from the pulse plethysmogram, has been proposed as a tool to assess nociception-antinociception balance. The relationship between SPI and autonomic nervous system (ANS) during general anesthesia is poorly understood and it is doubtful if SPI-guided analgesia may offer advantages over the standard clinical practice. The study was designed to evaluate if SPI-guided analgesia leads to a lower sympathetic modulation compared with standard clinical practice. METHODS: Electrocardiographic wave, non-invasive blood pressure and SPI were recorded in ASA I-II patients undergoing elective laparoscopic cholecystectomy, randomized to receive SPI-guided analgesia or standard analgesia. Hemodynamic parameters, SPI, mean and variance of heart rate, low (LF) and high frequency (HF) spectral components of heart rate variability were measured at four time points: (T0) baseline, (T1) after induction of general anesthesia, (T2) after pneumoperitoneum insufflation and (T3) after pneumoperitoneum withdrawal. RESULTS: SPI, hemodynamic and ANS parameters changed significantly in both groups during the study period (P<0.0001). At T2 SPI and markers of sympathetic modulation were significantly lower in SPI group (mean [SD] SPI 38.1 [15.3] vs. 48.1 [16.2] normalized units, P<0.05; LF 38 [8.6] vs. 56.2 [20.6] normalized units, P<0.01; LF/HF 1.01 [1.1] vs. 2.68 [2.07], P<0.01). There was no difference in remifentanil consumption, recovery time from anesthesia, or postoperative pain and complications. CONCLUSION: SPI-guided analgesia led to a more stable sympathetic modulation but didn't seem to offer clinically relevant advantages over the standard clinical practice for laparoscopic cholecystectomy.

Preoperative autonomic nervous system analysis may stratify the risk of hypotension after spinal anesthesia.

BACKGROUND: Studies on pregnant women undergoing cesarean delivery or elderly men scheduled for prostate brachytherapy have demonstrated the predictive value of heart rate variability (HRV) analysis for hypotension during spinal anesthesia. We conducted a prospective observational study to investigate if preoperative HRV analysis may have a role in identifying the risk of hypotension following spinal anesthesia in otherwise healthy patients. METHODS: The study investigated 47 ASA physical status I-II patients aged between 18-50 years that underwent subarachnoid anesthesia for lower abdominal or orthopedic scheduled surgery. ECG was recorded from all subjects before the subarachnoid block. We analysed the autonomic nervous system modulation, measured by HRV analysis. The variables that were be considered were preoperative HRV total power, low frequency (LF) and high frequency (HF) heart beat oscillations and LF/HF ratio. The LF/HF ratio was dichotomized according to the median for sensitivity analysis. The lowest arterial pressure value between spinal anesthesia and the end of surgery was recorded. RESULTS: The median LF/HF before anesthesia was 2.3. We considered two groups of 23 (LF/HF<2.3, group LOW) and 24 (LF/HF>2.3, group HIGH) patients respectively. Both groups had similar baseline demographic and hemodynamic variables. A high preoperative sympathetic outflow and loss of vagal modulation, as stated by LF/HF>2.3, was correlated with a relative risk of 7.7 (95%CI 1.04 to 56.6, p=0.023) of post-spinal hypotension. CONCLUSIONS: Preoperative analysis of autonomic nervous system modulation might be useful to stratify the risk of post-spinal hypotension and it might indicate the need for careful monitoring or prophylactic fluids.

Neurotransmitter basis of the behavioral effects of hallucinogens.

Indole and phenethylamine-type hallucinogenic drugs were studied in an FR-40 operant behavioral procedure programmed to quantify "pausing,"-a behavioral disruption somewhat specific to hallucinatory drug effects. LSD, DOM, DMT and mescaline showed a potency ratio to produce pausing that is well correlated with the hallucinatory potencies of these agents in man. Furthermore, combinations of the hallucinogens interact with potentiation to cause FR-40 pausing, whereas a variety of non-hallucinogenic psychoactive drugs failed to shift the dose-response patterns of pausing for DOM or LSD. Depletion of brain catecholamines by pretreatment with intraventricular 6-OHDA reduced baseline FR-40 rates and attenuated the disruptive effects of d-amphetamine, but failed to modify the dose-response patterns of indole and phenethylamine hallucinogens. On the other hand, pretreatment with intraventricular 5,7-DHT to deplete brain 5-HT potentiated the pause-producing effects of the hallucinogens, although the disruptive effects of phenobarbital were not altered by this pretreatment. Injection of 5,7-DHT into the medial forebrain bundle at the hypothalamic level slightly potentiated LSD, attenuated DOM, and did not affect the pausing produced by mescaline. Metergoline pretreatment shifted the LSD and DMT dose-response curves for pausing to the right by a factor of 2--3, but shifted the DOM and mescaline dose-response patterns to a much greater extent. Metergoline alone slightly increased FR-40 response rates and decreased pausing from baseline levels. The patterns of imparied FR-40 performance induced by d-amphetamine and phenobarbital were unaltered by pretreatment with metergoline. The indole and phenethylamine classes of hallucinogens appear to disrupt this behavior by an agonistic effect at central 5-HT receptors. However, the two classes of drugs may interact with brain 5-HT systems by somewhat different mechanisms.

Mechanisms of the initial treatment phenomenon to diazepam in the rat.

The initial treatment phenomenon (ITP) to diazepam was investigated using a conditioned suppression of drinking (CSD) paradigm. Female Sprague-Dawley rats were trained to a stable baseline of punished and unpunished responses in the CSD paradigm. In Experiment 1, a control group (1) received vehicle after the CSD session on each of seven drug test days, while group 2 was treated with 3.0 mg/kg diazepam IP after each of these sessions. On drug test days 8-12, diazepam was administered to both groups before the CSD session. Drug test days were separated by 2-3 days when the animals were untreated but performed in the CSD. Prior exposure to diazepam in group 2 after sessions 1-7 conditioned the animals so that a greater release in punished behavior was seen during sessions 8-12 than in the control group (1). In Experiment 2, one group (3) of rats was administered diazepam vehicle after the CSD session for 4 drug test days and another group (4) was injected with 5.6 mg/kg diazepam after the CSD session on these same days. On the next 4 drug test days both groups received diazepam before they performed in the CSD. An ITP was observed in both the control (3) and the drug-conditioned (4) group, although the ITP was less obvious in the conditioned group. After a 28-day period of CSD exposure without vehicle or drug treatments, 5.6 mg/kg diazepam was administered to both groups before the CSD session for an additional 8 drug test days.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for 5-HT2 receptor mediation in quipazine anorexia.

Doses of d-amphetamine (3.2 mg/kg), fenfluramine (10 mg/kg) and quipazine (8 mg/kg) cause a significant reduction in food intake during a 30-min daily feeding session in food-deprived rats. Pirenperone and ritanserin, 5-HT2 receptor antagonists, significantly blocked the anorectic effect of quipazine, while d-amphetamine and fenfluramine effects were not modified. Metergoline, a non-specific blocker of 5-HT receptors, significantly blocked the anorectic effects of fenfluramine and quipazine, but not the d-amphetamine effect. Pretreatment with alpha- and beta-adrenergic receptor antagonists (prazosin, propranolol and pindolol), dopamine receptor antagonists (haloperidol and pimozide), the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine, and the opioid receptor antagonist naloxone failed to modify the anorectic effects of all three agents, with the exception that quipazine-induced anorexia was significantly reduced by pimozide. These results suggest that the quipazine anorexia is largely mediating through 5-HT2 receptors, although the effect of pimozide remains to be explained. Consistent with previous studies, the fenfluramine effect appears to be mediated through 5-HT1B receptors. Receptors involved in the anorectic effect of higher doses of d-amphetamine are still unidentified by this analysis. Further investigation is required to define the mechanisms by which quipazine and larger doses of d-amphetamine bring about a reduced appetite for food.

Comparison of anti-conflict drug effects in three experimental animal models of anxiety.

A novel form of experimentally-induced conflict behavior based on the conditioned suppression of drinking (CSD) is described and compared with two conventional animal models of human anxiety--a modified Geller-Seifter and an Estes-Skinner (Conditioned Emotional Response) procedure. The CSD procedure offered significant advantages over the two operant procedures in that the session duration was short (10 min) and the acquisition of stable behavioral baselines was rapid (approximately 2 weeks). Like the more conventional procedures, the CSD paradigm permitted the simultaneous determination of drug effects on shock-suppressed and nonsuppressed responding as estimates of antianxiety and sedative properties, respectively. With the CSD procedure, the anticonflict profiles for the benzodiazepines were highly correlated with their relative clinical antianxiety potency. Therefore, the CSD procedure appears to be a valuable tool in screening for possible antianxiety agents as well as in the behavioral testing of mechanism of action hypotheses regarding such agents.

Lack of central 5-hydroxytryptamine influence on the anticonflict activity of diazepam.

This study examined the effects of various drug treatments (IP injections) proposed to modify central 5-hydroxytryptamine (5-HT) activity on a conditioned suppression of drinking behavior in water-deprived rats. The subjects were trained to drink their daily water requirement during a 10-min session. Intermittent tone periods of 7 s were then introduced, the last 5 s of which the drinking tube was electrified. The animals gradually suppressed tube contacts during the tone to a low constant level within 2 weeks of training. Diazepam increased punished responding dramatically. The 5-HT antagonists methysergide (1 - 18 mg/kg), cyproheptadine (1 - 18 mg/kg), metergoline (0.25 - 2.0 mg/kg) and cinanserin (10 - mg/kg) failed to induce large, reliable increases in punished responding. When a low dose of diazepam was combined with 5-HT antagonists, only one treatment, methysergide at 3 mg/kg, potentiated the anticonflict activity of diazepam. Acute or chronic treatment with PCPA increased behavior suppressed by punishment, but this effect was weak, brief, and poorly related to the depletion of brain 5-HT. LSD (0.3 - 100 microgram/kg) administered 1, 10, or 30 min before the test was ineffective in overcoming suppression by punishment. Mescaline (6 - 30 mg/kg) had no significant effect on punished responding. 5-HTP (18 mg/kg) decreased the number of shocks accepted, but not after pretreating with carbidopa. Pretreatment with carbidopa plus 5-HTP potentiated the anticonflict effect of diazepam. The 5-HT agonist mCPP (0.25 - 2.0 mg/kg) enhanced suppression due to punishment, but only in doses that interfered with unpunished responding. The 5-HT-releasing agent fenfluramine (0.25 - 1.0 mg/kg) did not affect this behavior. Amitriptyline pretreatment in a dose not affecting unpunished behavior (5.6 mg/kg) potentiated the diazepam-induced increase in punished responding. These results are difficult to reconcile with the proposal that suppression of behavior consequent to punishment is related to brain 5-HT activity.

Developmental effects of early postnatal treatment of rats with prochlorperazine.

This study examined effects of neonatal prochlorperazine in rats tested as adults in a variety of behaviors. The drug exposure impaired open field behavior during treatment neonatally. However, no differences in open field behavior were observed in adulthood. Adult females that had received drug were less efficient in obtaining food reinforcement in a conditioned maze performance than were respective controls and showed a slight increase in motor activity during accommodation. d-Amphetamine-induced motor activity was greater in both treated males and females relative to respective controls. Spaced trials in shuttle-box avoidance uncovered an avoidance decrement in the treated females only. This drug treatment appears to cause subtle changes in brain development in the rat.

Chronic haloperidol treatment: effects on operant responding and inter-response time.

Three groups (n = 6) of male Sprague-Dawley rats were trained to barpress for food reinforcement on a fixed ratio-40 schedule. Each group then received one of three doses of haloperidol (0.125, 0.25, or 0.5 mg/kg, i.p.) according to the following treatment regimen: Baseline, Presession, Postsession, Presession, Postsession, Baseline, Extinction. Each treatment lasted six days each. Only the Presession and Extinction conditions resulted in a significant decrease in the number of reinforcements earned. The number of inter-response times greater than ten sec was inversely related to the number of reinforcements earned. The fact that chronic presession, but not postsession treatment, significantly decreased the number of reinforcements earned would favor an anhedonia interpretation over one postulating cumulative motor deficits. In any event, prior concurrent experience with the drug effect and the operant behavior appears to be critical to the decrement induced by haloperidol.

Diazepam-ethanol interaction: initial treatment and combined treatment effects.

Water-deprived female Sprague-Dawley rats were trained in a conditioned suppression of drinking paradigm. Experiment 1 assessed the effects of prior experience with ethanol on the initial treatment deficit of diazepam (1A) and the influence of prior experience with diazepam on the initial treatment effects of ethanol (1B). In Experiment 1A, half the animals received three daily doses of ethanol, while the other half received vehicle for 3 days. All rats then received vehicle followed by 3 days of ethanol treatment. No significant effect of prior experience with ethanol was observed on the diazepam initial treatment deficit. In Experiment 1B, half the animals received vehicle followed by three daily doses of diazepam, while the other half received vehicle. All subjects then received vehicle followed by 3 days of ethanol treatment. No significant effect of prior experience with diazepam was noted on ethanol's initial treatment effects. Experiment 2 assessed the effects of diazepam (0, 1, 2, and 4 mg/kg) and ethanol (0, 0.5, 1 and 2 g/kg) alone and in combination in the conflict test. Diazepam, administered alone, resulted in an antipunishment effect. Ethanol alone did not produce an antipunishment effect. The combination of the two drugs generally decreased both punished and unpunished responding. Further, the CNS depressant effects of these drugs appear to be additive. The qualitative effects of these two drugs are different enough to disallow generalization to each other in a conflict test.

Effect of perinatal polybrominated biphenyl exposure on acquisition and performance of an autoshaping paradigm.

Pregnant Sprague-Dawley rats received oral doses of 0, 0.2 or 2 mg/kg/day polybrominated biphenyls (PBB) as fireMaster BP-6 (BP-6) from day 6 of gestation through day 24 postpartum. At approximately 6 months of age male and female offspring were food-deprived to 80% of their free-feeding weights and subjected to four phases of an autoshaping paradigm. Acquisition of Phase I, a VI-90 second schedule of responding, was significantly delayed for female offspring from dams administered 2 mg/kg/day BP-6; a trend toward delayed acquisition was observed in all other PBB-exposed animals. No BP-6-related difference in latency to respond during this phase was observed. Male offspring from dams administered BP-6 appeared to acquire Phase II responding (a FI-90 second contingency) at a faster rate than did control males. In contrast, BP-6-exposed females acquired Phase II responding at a somewhat slower rate than did control females. The sex-related difference in responding may involve a rate-dependent influence, as control females acquired Phase II responding much more quickly than did control males. Control males and females acquired Phase III (FR-20 responding) at approximately the same rate. No BP-6-related deficits were observed during the initial few days of acquisition of FR-20 responding. However, BP-6-exposed male offspring tended to respond more than did control males after this time. BP-6-exposed females tended to respond less than did control females only as the responding of controls approached an asymptote. Phase IV involved FR-20 responding following challenge with d-amphetamine or chloral hydrate; no significant BP-6-related changes in disruption of this behavior were observed.