Sprague Dawley rats from different vendors vary in the modulation of prepulse inhibition of startle (PPI) by dopamine, acetylcholine, and glutamate drugs.

RATIONALE: Rodent vendors are often utilized interchangeably, assuming that the phenotype of a given strain remains standardized between colonies. Several studies, however, have found significant behavioral and physiological differences between Sprague Dawley (SD) rats from separate vendors. Prepulse inhibition of startle (PPI), a form of sensorimotor gating in which a low-intensity leading stimulus reduces the startle response to a subsequent stimulus, may also vary by vendor. Differences in PPI between rat strains are well known, but divergence between colonies within the SD strain lacks thorough examination. OBJECTIVES: We explored intrastrain variation in PPI by testing SD rats from two vendors: Envigo and Charles River (CR). METHODS: We selected drugs acting on four major neurotransmitter systems that have been repeatedly shown to modulate PPI: dopamine (apomorphine; 0.5, 1.5, 3.0 mg/kg), acetylcholine (scopolamine; 0.1, 0.5, 1.0 mg/kg), glutamate (dizocilpine; 0.5, 1.5, 2.5 mg/kg), and serotonin (2,5-Dimethoxy-4-iodoamphetamine, DOI; 0.25, 0.5, 1.0 mg/kg). We determined PPI and startle amplitude for each drug in male and female Envigo and CR SD rats. RESULTS: SD rats from Envigo showed dose-dependent decreases in PPI after apomorphine, scopolamine, or dizocilpine administration, without significant effects on startle amplitude. SD rats from CR were less sensitive to modulation of PPI and/or more sensitive to modulation of startle amplitude, across the three drugs. CONCLUSIONS: SD rats showed vendor differences in sensitivity to pharmacological modulation of PPI and startle. We encourage researchers to sample rats from separate vendors before experimentation to identify the most suited source of subjects for their specific endpoints.

Handling prevents and reverses cognitive deficits induced by sub-chronic phencyclidine in a model for schizophrenia in rats.

Treatments for schizophrenia are not effective in ameliorating cognitive deficits. Therefore, novel therapies are needed to treat cognitive impairments associated with schizophrenia (CIAS), which are modelled in rats through administration of sub-chronic phencyclidine (scPCP). We have previously shown that enrichment via voluntary exercise prevents and reverses impairments in novel object recognition (NOR) in this model. The present study aimed to investigate if handling could prevent delay-induced NOR deficits and prevent and reverse scPCP-induced NOR deficits. Two cohorts of adult female Lister Hooded rats were used. In experiment one, handling (five minutes/day, five days/week for two weeks), took place before scPCP administration (2 mg/kg, i.p. twice-daily for seven days). NOR tests were conducted at two, four, and seven weeks post-handling with a one-minute inter-trial interval (ITI) and at five weeks post-dosing with a six-hour ITI. In experiment two, rats were handled after scPCP administration and tested immediately in the one-minute ITI NOR task and again at two weeks post-handling. In both handling regimens, the scPCP control groups failed to discriminate novelty, conversely the scPCP handled groups significantly discriminated in this task. In the 6 h ITI test, vehicle control and scPCP control failed to discriminate novelty; however, the vehicle handled and scPCP handled groups did significantly discriminate. Handling rats prevented and reversed scPCP-induced deficits and prevented delay-induced NOR deficits. These findings add to evidence that environmental enrichment is a viable treatment for cognitive deficits in rodent tests and models of relevance to schizophrenia, with potential to translate into effective treatments for CIAS.

Trauma-informed Approaches to Substance Use Interventions with Indigenous Peoples: A Scoping Review.

Indigenous Peoples experience disproportionately higher rates of problematic substance use. These problems are situated in a context of individual and intergenerational trauma from colonization, residential schools, and racist and discriminatory practices, policies, and services. Therefore, substance use interventions need to adopt a trauma-informed approach. We aimed to synthesize and report the current literature exploring the intersection of trauma and substance use interventions for Indigenous Peoples. Fourteen databases were searched using keywords for Indigenous Peoples, trauma, and substance use. Of the 1373 sources identified, 117 met inclusion criteria. Literature on trauma and substance use with Indigenous Peoples has increased in the last 5 years (2012-2016, n = 29; 2017-2021, n = 48), with most literature coming from the United States and Canada and focusing on historical or intergenerational trauma. Few articles focused on intersectional identities such as 2SLGBTQIA+ (n = 4), and none focused on veterans. There were limited sources (n = 25) that reported specific interventions at the intersection of trauma and substance use. These sources advocate for multi-faceted, trauma-informed, and culturally safe interventions for use with Indigenous Peoples. This scoping review illuminates gaps in the literature and highlights a need for research reporting on trauma-informed interventions for substance use with Indigenous Peoples.

An inhibitor of methionine aminopeptidase type-2, PPI-2458, ameliorates the pathophysiological disease processes of rheumatoid arthritis.

OBJECTIVE: To elucidate the role of methionine aminopeptidase type-2 (MetAP-2) in the clinical pathology of rheumatoid arthritis, arthritis was induced in rats by administration of peptidoglycan-polysaccharide (PG-PS). DESIGN: The inhibitor of MetAP-2, PPI-2458, was administered orally at 5 mg/kg every other day during 3 distinct phases of the disease. In vitro studies were performed to clarify in vivo findings. RESULTS: Ankle swelling was completely alleviated by MetAP-2 inhibition. Inhibition of MetAP-2 in blood and tissues correlated with protection against PG-PS-induced arthritis. Histopathology of the tarsal joints improved following PPI-2458 administration, including a significant improvement of bone structure. In in vitro studies, osteoclast formation and activity were inhibited by PPI-2458, a mechanism not previously attributed to MetAP-2 inhibition. CONCLUSIONS: The important role that MetAP-2 has in the pathophysiological disease processes of PG-PS arthritis provides a strong rationale for evaluating PPI-2458 as a disease modifying antirheumatic treatment for rheumatoid arthritis.

Discussions in the home about sex: different recollections by parents and children.

University students and their parents were asked whether they had ever had a meaningful discussion about sex. More than half of the students answered No, yet in 60% of these cases, one or both parents said that there had been meaningful discussions. Students and their parents most frequently disagreed about the topics of sexually transmitted diseases, sexual intercourse, reproduction, birth control, homosexuality, and sexual abuse. Mothers were more likely than fathers to have had discussions that daughters considered to be meaningful, and as likely as fathers in the case of sons. Parents who indicated that they had had meaningful discussions about sex with their parents while growing up were much more likely than other parents to have had discussions that their own children recognized as meaningful. Nevertheless, the results demonstrate that many parents greatly underestimate the extent of factual information that their children wish to learn about sexuality.

Allergy to human seminal fluid: characterization of the allergen and experience with immunotherapy.

A 20-year-old woman was observed with a history of a severe generalized systemic reaction after topical contact with seminal fluid. A prick test with undiluted seminal fluid produced a 5.0 mm wheal-and-flare response with pseudopods. Prick tests with saliva and serum from the same source as the seminal fluid were negative. Measurement of IgE antibody to seminal-fluid allergen with a Biotin-Avidin ELISA technique yielded strong activity. No IgG antibody could be detected. Significant prick test reactivity could be found in Sephadex G-100 fractions that had a molecular weight range of 12,000 to 75,000 daltons and that contained approximately 5% of the total protein in the starting material. Isoelectric focusing fractions with strong skin test reactivity had a pI range of 5.4 to 6.6. These fractions contained one major protein band. Immunotherapy was conducted with a Sephadex fraction of seminal fluid during a 24-month period. A cumulative dose of 32 mg of protein was administered. No side effects other than local swelling occurred. Ten months after the start of immunotherapy, IgE antibody became unmeasureable, an effect that was demonstrated not due to the inhibitory effect of IgG antibody. IgG antibody rose progressively in this period. Clinically, the patient became less sensitive to topical contact. Although the natural history of seminal-fluid allergy is not known, immunotherapy may be effective.

Cat allergen content of commercial house dust extracts: comparison with dust extracts from cat-containing environment.

Eighteen lots of house dust extract from nine commercial sources (obtained as weight per volume or protein nitrogen unit per cubic centimeter) were analyzed for cat allergen content by direct quantitative immunoelectrophoresis after concentration. Cat allergen 1 was measurable (greater than 0.3 units) in 11 extracts with a mean (range) of 5.8 (1.3 to 31.0) U/gm of source material. Cat albumin was measurable (greater than 2.4 units) in 12 extracts with a mean (range) of 53.4 (11.5 to 319.7) U/gm. In order to evaluate whether the cat allergen 1 content is a significant contribution to the allergenic activity of the extract, 17 cat-allergic subjects were tested by prick test with a purified preparation of cat allergen 1. The mean (range) concentration that produced a 3 mm wheal was 0.01 (0.0013 to 1.33) U/ml. Therefore, the commercial house dust extracts studied, when these extracts were diluted to a concentration commonly used for prick testing, would frequently contain enough cat allergen 1 to produce strong prick test reactions in cat-allergic subjects. It is difficult to justify the use of such commercial dust extracts as diagnostic reagents. For comparison purposes, nine dust samples from an apartment housing two cats were similarly analyzed. Cat allergen 1 was measurable in seven samples with a mean (range) of 23.8 (1.8 to 64.3) U/gm. Cat albumin could be measured in all nine samples with a mean (range) of 32.3 (0.16 to 70.8) U/gm. The average amount of cat allergen 1 that could be washed off the surface of the cats was 270 units. Large reservoirs of cat allergen 1 were present.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunologic and biochemical properties of the major mouse urinary allergen (Mus m 1).

Rabbit antiserum to the mouse major urinary protein identified a single antigen that was also found in mouse serum and pelt extract. The skin test reactivity of mouse-pelt extract and mouse urine in two mouse-allergic subjects was significantly reduced after immunoabsorption with the gamma globulin fraction of this antiserum. The antigen defined by this antiserum was designated mouse allergen 1 (MA1). An immunoelectrophoretic procedure was set up to measure its concentration. MA1 had a molecular weight of approximately 19,000 on Sephadex gel filtration and 18,000 to 21,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Isoelectric focusing identified at least four bands with antigenic activity; the major band had an isoelectric point of 3.9. Significant antigenic and allergenic activity of MA1 was retained on reduction and digestion with papain and pepsin. Heating at 90 degrees C for periods up to 180 minutes resulted in a progressive loss, but not abolition, of activity. Serum and urine derived from male mice contained approximately fourfold more MA1 than samples derived from female mice. Urine contained at least 100-fold more MA1 than serum. Of the tissue extracts studied, liver extract had the highest amount of MA1. The immunochemical properties of MA1, its tissue distribution, and sex differences in its concentration provide strong evidence that MA1 is identical to the previously described mouse major urinary protein.