Biomedical subjects

B J Johnson

Publications and source records attributed to B J Johnson.

At least 55 records · Page 3Linked to original sources

PubMed1998

Activation state of muscle satellite cells isolated from steers implanted with a combined trenbolone acetate and estradiol implant.

Muscle satellite cells were isolated from seven yearling steers implanted for 31 d with a combined implant that contained 120 mg of trenbolone acetate (TBA) and 24 mg of estradiol (E2) and from seven nonimplanted, control steers. Implanted steers had a 28% greater ADG and a 23% greater feed efficiency than did nonimplanted steers. Implanted steers had increased (P<.001) circulating IGF-I concentrations on d 6, 14, and 31 after implantation, and circulating IGF-I concentrations in control steers remained constant or decreased (P<.05) at these times. Maximum fusion percentage was greater (P< .005) in satellite cell cultures isolated from implanted steers (ISC cultures) than in satellite cell cultures isolated from control steers (NSC cultures) (72.8% vs 54.8%, respectively). Satellite cell cultures isolated from implanted steers (ISC cultures) also contained a greater (P<.001) number of myotube nuclei than did NSC cultures (7,998 nuclei/cm2 vs 5,150 nuclei/cm2, respectively). After 72 h in culture, the number of cells (corrected for plating density) was 43% greater (P<.05) in ISC cultures than in NSC cultures. [3H]Thymidine incorporation rates per 10(5) cells at 24 and 34 h after plating were greater (P<.05) in ISC cultures than in NSC cultures; however, incorporation rates did not differ at 72 h. These data indicate that TBA + E2 implantation may result in an in vivo activation of muscle satellite cell proliferation that can be detected in cell culture. This activation may play an important role in TBA + E2-enhanced muscle growth.

Anabolic Agents↗

PubMed1998

Effect of a combined trenbolone acetate and estradiol implant on steady-state IGF-I mRNA concentrations in the liver of wethers and the longissimus muscle of steers.

Treatment of lambs (initial BW 28 kg) for 24 d with a combined implant containing 40 mg of trenbolone acetate (TBA) and 8 mg of estradiol (E2) increased ADG 25% (P < .05, n = 8) and feed efficiency 23% (P < .05, n = 2) compared with unimplanted lambs. By d 3 following implantation, sera from wethers implanted with TBA + E2 showed 32% (307 vs 233 ng/mL) increases (P < .001, n = 8) in IGF-I concentration compared with sera from unimplanted wethers. This increase was maintained throughout the entire 24-d study. Steady-state hepatic IGF-I mRNA levels were increased approximately 150% in implanted lambs compared with unimplanted lambs (P < .05, n = 4). These data suggest that liver may be the source of at least part of the increased circulating IGF-I in TBA + E2-implanted sheep. In steers implanted with Revalor-S (120 mg of TBA and 24 mg of E2) for 40 d, the steady-state concentration of IGF-I mRNA in the longissimus muscle was 68% greater than in the longissimus muscle of unimplanted steers (P = .013, n = 4). Consequently, increased local production of IGF-I by muscle tissue may play a role in increasing circulating IGF-I concentrations as well as an autocrine or paracrine role in stimulating muscle growth in steers implanted with Revalor-S.

Anabolic Agents↗

PubMed1998

Hoof size, shape, and balance as possible risk factors for catastrophic musculoskeletal injury of Thoroughbred racehorses.

OBJECTIVE: To evaluate hoof size, shape, and balance as risk factors for catastrophic musculoskeletal injuries (CMI), including suspensory apparatus failure (SAF) and cannon bone condylar fracture (CDY) in Thoroughbred racehorses. ANIMALS: 95 Thoroughbred racehorses that died between 1994 and 1996. PROCEDURE: 38 quantitative measures of hoof size, shape, and balance were obtained from orthogonal digital images of the hoof and were compared between case horses with forelimb CMI (70), SAF (43), and CDY (10) injuries and control horses whose death was unrelated to the musculoskeletal system (non-CMI, 25). Comparison of group means between cases and controls was done using ANOVA, and multivariable logistic regression was used to estimate odds ratios. RESULTS: Odds of CMI were 0.62 times lower for a 5mm increase in ground surface width difference and 0.49 times lower for a 100-mm2 increase in sole area difference. Odds of SAF were 6.75 times greater with a 10 degrees increase in toe-heel angle difference and 0.58 times lower with a 100-mm2 increase in sole area difference. Odds of CDY were 0.26 times lower with a 3 degrees increase in toe angle, 0.15 times lower with a 5-mm increase in lateral ground surface width, and 0.35 times lower with a 100-mm2 increase in sole area difference. CLINICAL RELEVANCE: Decreasing the difference between toe and heel angles should decrease risk of SAF for Thoroughbred racehorses and should be considered in addition to increasing toe angle alone to help prevent catastrophic injury. Trimming the hoof to perfect mediolateral symmetry may not be a sound approach to avoiding injury.

Animals↗

PubMed1997

rhuIL-2 adjunctive therapy in multidrug resistant tuberculosis: a comparison of two treatment regimens and placebo.

SETTING: Low-dose recombinant human interleukin 2 (rhuIL-2) adjunctive immunotherapy in multidrug resistant tuberculosis (MDR-TB) patients. OBJECTIVE: Evaluation of the effects of daily versus pulse-administered rhuIL-2 compared to placebo. DESIGN: MDR-TB patients on best available antituberculous chemotherapy received rhuIL-2 for 30 consecutive days (daily therapy), or for 5 days followed by a 9-day 'rest', for three cycles (pulse therapy). Placebo control patients received diluent. The cumulative total dose of rhuIL-2 given to each patient in either rhuIL-2 treatment group was the same. Patient immunologic, microbiologic, and radiologic responses were compared. RESULTS: The three treatment schedules induced different results. Immune activation was documented in patients receiving daily rhuIL-2 therapy. Numbers of CD25+ and CD56+ cells in the peripheral blood were increased in these patients, but not in patients receiving pulse rhuIL-2 or placebo. In addition, 5/8 (62%) patients receiving daily rhuIL-2 demonstrated reduced or cleared sputum bacterial load while only 2/7 (28%) pulse rhuIL-2 treated and 2/8 (25%) controls showed bacillary clearance. Chest radiographs of 7/12 (58%) patients receiving daily rhuIL-2 indicated significant improvement over 6 weeks. Only 2/9 (22%) pulse rhuIL-2-treated patients and 5/12(42%) placebo controls showed radiologic improvement. CONCLUSION: Daily low dose rhuIL-2 adjunctive treatment stimulates immune activation and may enhance the antimicrobial response in MDR-TB.

Adult↗

PubMed1997

Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic.

Animal studies have shown an exponential increase in the risk of Borrelia burgdorferi infection after 48-72 h of deer tick attachment. Persons with tick bites were prospectively studied to determine if those with prolonged tick attachment constitute a high-risk group for infection. Ticks were identified, measured for engorgement, and assayed by polymerase chain reaction (PCR) for B. burgdorferi DNA. Duration of attachment was determined from the scutal index of engorgement. Of 316 submissions, 229 were deer ticks; 14% were positive by PCR. Paired sera and an intact tick for determination of duration of attachment were available for 105 subjects (109 bites). There were 4 human cases (3.7% of bites) of B. burgdorferi infection. The incidence was significantly higher for duration of attachment > or =72 h than for <72 h: 3 (20%) of 15 vs. 1 (1.1%) of 94 (P = .008; odds ratio, 23.3; 95% confidence interval, 2.2-242). PCR was an unreliable predictor of infection. Tick identification and measurement of engorgement can be used to identify a small, high-risk subset of persons who may benefit from antibiotic prophylaxis.

Animals↗

PubMed1997

Genetic heterogeneity of Borrelia burgdorferi in the United States.

To examine in detail Borrelia burgdorferi strain diversity in the United States, 186 isolates from human, tick, and rodent sources were analyzed from multiple distinct geographic regions of the United States and abroad. Strains were characterized by genomic macrorestriction analysis and ospA and 23S rDNA gene sequencing followed by phylogenetic analysis. Results indicate that spirochetal isolates from the United States fall into two major divisions and nine or more subdivisions; human isolates fell into five of these subdivisions. Greater genetic diversity was observed among B. burgdorferi isolates from moderate climatic regions, consistent with increased tick vector and reservoir diversity. All of the Borrelia isolates were reactive by ospA polymerase chain reaction except for Borrelia hermsii controls and several tick isolates from the Northeast, which were shown to lack the 49-kb plasmid encoding outer surface protein A (OspA). The data suggest that US B. burgdorferi isolates demonstrate substantial genetic heterogeneity, with regional differences in spirochete populations.

Animals↗

PubMed1997

Cell-density-dependent expression of Borrelia burgdorferi lipoproteins in vitro.

Previously, we had identified non-OspA-OspB surface proteins of Borrelia burgdorferi that are targeted by the antibody-dependent complement-mediated killing mechanism. Here we demonstrate by Western blotting that one of these proteins, P35, is upregulated at the onset of stationary phase in vitro. Northern analysis revealed that the upregulation of P35 is at the level of transcription. In addition, the expression of an open reading frame (ORF) located downstream of the p35 gene was found to be regulated in the same fashion as that of P35. This ORF encodes a 7.5-kDa lipoprotein. The transcriptional start sites for both of these genes were determined, to aid in the identification of the putative promoter regions. Additional sequencing of the 5' flanking region of the p35 gene revealed a region of dyad symmetry 52 bp upstream of the transcription start site. Southern analysis demonstrated that the expression of these genes was not due to a cell-density-dependent rearrangement in the genome of B. burgdorferi. These findings provide an in vitro model for studying mechanisms of gene regulation in B. burgdorferi.

Amino Acid Sequence↗

PubMed1997

Molecular characterization of a 35-kilodalton protein of Borrelia burgdorferi, an antigen of diagnostic importance in early Lyme disease.

Antibodies against a 35-kDa antigen of Borrelia burgdorferi are detectable in the serum of about half of patients with early Lyme disease. The gene encoding this antigen was isolated from a genomic library of B. burgdorferi B31 (low passage), and full-length expression of the recombinant gene product was achieved in Escherichia coli. Antiserum raised against the recombinant protein was reactive with a B. burgdorferi protein of the same molecular size as the diagnostic 35-kDa antigen cited in an earlier study of criteria for the sero-diagnosis of early Lyme disease. Also, the recombinant protein was reactive with serum from patients with early Lyme disease who were seropositive for the 35-kDa antigen. DNA sequence analysis of the gene indicated an open reading frame of 909 bp encoding a protein with a calculated molecular mass of 34.3 kDa. This gene did not possess the usual initiation codon ATG but rather probably used a TTG codon. The deduced amino acid sequence of the N terminus exhibited a motif similar to that for signal peptides of lipoproteins. Southern blotting revealed a chromosomal location for this gene; and it was specific for B. burgdorferi, B. afzellii, and B. garinii but not for B. hermsii, B. coriaciae, or B. turicatae.

Amino Acid Sequence↗

PubMed1997

Culturing selects for specific genotypes of Borrelia burgdorferi in an enzootic cycle in Colorado.

In Colorado, Borrelia burgdorferi sensu stricto, the etiologic agent of Lyme disease, is maintained in an enzootic cycle between Ixodes spinipalpis ticks and Neotoma mexicana rats (27). The frequencies of flagellin (fla), 66-kDa protein (p66), and outer surface protein A (ospA) alleles were examined in 71 B. burgdorferi isolates from samples from Colorado. Approximately two-thirds of these samples were isolates from I. spinipalpis ticks that had been cultured in BSK-H medium prior to DNA extraction. The remaining samples were from total DNA extracted directly from infected I. spinipalpis ticks. A portion of each gene was amplified by PCR and screened for genetic variability by single-strand conformation polymorphism (SSCP) analysis. We identified three alleles in the fla gene, seven in the p66 gene, and seven in the ospA gene. Sequencing verified that the amplified products originated from B. burgdorferi template DNA and indicated 100% sensitivity and specificity of the SSCP analysis. The frequencies of the p66 and ospA alleles were significantly different between cultured and uncultured spirochetes. The number of three-locus genotypes and the genetic diversity of alleles at all loci were consistently lower in cultured spirochetes, suggesting that culturing of B. burgdorferi in BSK-H medium may select for specific genotypes.

Alleles↗

PubMed1996

Fatal musculoskeletal injuries incurred during racing and training in thoroughbreds.

OBJECTIVE: To characterize and contrast data from Thoroughbreds that incurred a fatal musculoskeletal injury (FMI; injury resulting in death or euthanasia) during racing or training and data from all California race entrants during a 9-month period in 1991. DESIGN: Case-control study. ANIMALS: Thoroughbreds that incurred a FMI during racing or training at a California race-meet and all California race entrants from January through June and October through December 1991. PROCEDURE: Age and sex were compared with chi 2 and Fisher's exact tests among horses fatally injured while racing and training. A log-linear model was fit to assess the relationship between race-meet and age and sex of California race entrants. Incidence risk of racing FMI was estimated per 1,000 race entrants, and the relationship between the occurrence of FMI during racing with race-meet, age, and sex was evaluated by logistic regression. RESULTS: Injury type and sex-specific age distributions differed among the horses fatally injured during racing and training. Age and sex distributions of the race entrants were not independent and varied among race-meets. Overall incidence risk of racing FMI was estimated at 1.7/1,000 race entrants. Risk of racing FMI in male horses was about twofold that in female horses, and in 4-year-olds was twofold that in 3-year-olds. CLINICAL IMPLICATIONS: Age and sex-related differences in risk of incurring a FMI during racing should be considered when comparing fatal injury rates among race-meets.

Age Distribution↗

PubMed1996

Serodiagnosis of Lyme disease: accuracy of a two-step approach using a flagella-based ELISA and immunoblotting.

An ELISA containing a purified flagellar antigen from Borrelia burgdorferi (FLA-ELISA) was evaluated. The FLA-ELISA, detecting IgM and IgG together, did not have adequate specificity by itself. Good accuracy was obtained, however, when the FLA-ELISA was the first step in a two-step protocol that used immunoblotting as a conditional second test. Samples that scored positive or equivocal by the FLA-ELISA were evaluated with separate IgM and IgG immunoblots. The sensitivity of the two-step process for patients with erythema migrans or with later manifestations of Lyme disease was 64% and 100%, respectively. The specificity for health blood donors was 100% and was 90% for the aggregate of all persons with illness that may cause serologic cross-reactivity (98% if the samples from relapsing fever patients were excluded). Test precision was 96% overall, 99% for Lyme disease case serum samples, 100% for specimens from blood donors, and 88% for samples from persons with other illness.

Antigens, Bacterial↗

PubMed1996

Outer surface protein C (OspC), but not P39, is a protective immunogen against a tick-transmitted Borrelia burgdorferi challenge: evidence for a conformational protective epitope in OspC.

Outbred mice were immunized with the soluble fraction of a crude Escherichia coli lysate containing either recombinant outer surface protein C (OspC or P39 of Borrelia burgdorferi B31 (low passage). Following seroconversion, the mice were challenged with an infectious dose of B. burgdorferi B31 via the natural transmission mode of tick bite. Three mice immunized with P39 were not protected; however, all 12 of the recombinant OspC-immunized mice were protected from infection as assayed by culture and serology. Although OspC has been shown to be a protective immunogen against challenge with in vitro-cultured borrelia administered by needle, this study is the first to demonstrate OspC effectiveness against tick-borne spirochetes. Following feeding, all ticks still harbored B. burgdorferi, suggesting that the mechanism of protection is not linked to destruction of the infectious spirochete within the tick. In a separate experiment, groups of four mice were immunized with protein fractions from B. burgdorferi B31 purified by preparative gel electrophoresis in an attempt to identify potential protective antigens. Many of these mice developed high-titer-antibody responses against OspC, but curiously the mice were susceptible to B. burgdorferi infection via tick bite. These results suggest that the protective epitope(s) on OspC is heat sensitive/conformational, a finding which has implications in vaccine development.

Animals↗

PubMed1996

Effect of a combined trenbolone acetate and estradiol implant on feedlot performance, carcass characteristics, and carcass composition of feedlot steers.

Objectives of this study were to determine the influence of trenbolone acetate (TBA) and estradiol (E2) in a combined implant on feedlot performance, carcass characteristics, and carcass composition in finishing steers. Sixty-four large-framed (394.1 kg) crossbred steers were randomly assigned to one of four pens. Subsequently, pens were randomly assigned to one of two treatments, implanted (120 mg of TBA and 24 mg of E2) and nonimplanted. Eight steers/treatment were slaughtered for initial carcass composition. Remaining steers were assigned to one of three serial slaughter dates (d 40, 115, or 143). Implantation increased circulating trenbolone (TBOH) and E2 concentrations throughout the trial. Implantation increased ADG 18% (P < .001) during d 0 to 40, 21% (P < .001) from d 0 to 115, and 16% for the entire 143 d. Implant status had no effect (P > .05) on dry matter intake. Feed efficiency was improved 13% during d 0 to 40 (P < .01) and from d 41 to 115 (P = .07). Longissimus muscle area was larger (P < .05) in implanted steers than in nonimplanted steers on d 115. Carcasses from implanted steers had a smaller (P < .05) percentage of kidney, pelvic, and heart (KPH) fat on d 143 than those from nonimplanted steers. Carcasses from implanted steers possessed more carcass protein (P < .05) on d 40. Implanted steers had an 82% increase (P < .05) in daily carcass protein accretion during the first 40 d. Implantation increased (P < .01) carcass water but did not affect carcass fat accumulation throughout the feeding period. The combined TBA+E2 implant improved feedlot performance and stimulated carcass protein accretion in feedlot steers.

Anabolic Agents↗

PubMed1996

Stimulation of circulating insulin-like growth factor I (IGF-I) and insulin-like growth factor binding proteins (IGFBP) due to administration of a combined trenbolone acetate and estradiol implant in feedlot cattle.

Objectives of this study were to analyze alterations in circulating IGF-I and insulin-like growth factor binding protein (IGFBP) concentrations due to administration of a combined trenbolone acetate (TBA) and estradiol (E2) implant. This study was part of a larger serial slaughter study in which 64 large-framed (394.1 kg) crossbred steers were randomly assigned to one of four pens. Pens were assigned to one of two treatments: implanted (120 mg of TBA and 24 mg of E2) and nonimplanted. After d 2, 24 steers/treatment remained on the study. These steers were assigned to one of three serial slaughter dates (d 40, 115, and 143). Blood samples were obtained on d 0, 2, 21, 40, 115, and 143 from remaining steers. Serum was harvested and analyzed for IGF-I, IGFBP, and mitogenic activity. Glycyl-glycine (GG) extraction of serum was performed to reduce IGFBP interference in the IGF-I RIA. Implantation with TBA+E2 interference in the IGF-I RIA. Implantation with TBA+E2 increased (P < .001) circulating IGF-I concentrations during the period from d 0 to d 40. On d 21 and 40, steers implanted with TBA+E2 had 16 and 22%, respectively, greater (P < .001) circulating IGF-I concentrations than nonimplanted steers. For steers in the study for at least 115 d, TBA+E2 increased (P < .05) IGF-I concentrations 9, 13, and 19% on d 21, 40, and 115, respectively, compared with nonimplanted steers. Implantation with TBA+E2 resulted in greater (P < .05) serum concentration of a 49/39-kDa IGFBP (IGFBP-3) on d 21 and 40 after implantation. Sera from steers implanted with TBA+E2 stimulated proliferation of cultured muscle satellite cells to a greater extent (P < .05) than did sera from nonimplanted steers on d 21, 40, 115, and 143 after implantation. In summary, TBA+E2 increased serum concentrations of both IGF-I and IGFBP-3. Additionally, implantation increased mitogenic activity of sera from implanted as compared to nonimplanted steers. These alterations may be partially responsible for the positive effects of TBA+E2 implants on feedlot performance and rate of protein accretion in steers.

Anabolic Agents↗

PubMed1996

Postmortem evaluation of homotypic variation in shoe characteristics of 201 thoroughbred racehorses.

OBJECTIVES: To develop a standard technique for evaluation of racehorse shoes, to assess homotypic variation (interlimb variation) in shoe characteristics, and to determine whether shoe characteristics varied with age and sex. DESIGN: Cross-sectional study. ANIMALS: Thoroughbred racehorses (n = 201) that died or were euthanatized at California racetracks between August 1992 and July 1994. PROCEDURE: Shoe characteristics were measured on horses examined after death. Percentage of agreement was used to compare shoe characteristics between limbs (homotypic variation). Using chi 2 analysis, shoe characteristics were compared between horses grouped by age and sex. RESULTS: Toe grabs were present on 90.5% of horses, and rim shoes were present on 15.9% of horses. Heel traction devices were less frequent on front (2.5%) than rear (6%) hooves. Pads were present on 24.9% of horses, with bonded rim pads most common. Special types of shoes were present cn 5% of horses. Percentage of agreement between left and right front hooves and between left and right rear hooves was high (20/25 variables; % agreement > or = 99). In contrast, percentage of agreement between left front and left rear hooves and between right front and right rear hooves was low (2/25 variables; % agreement > or = 99). Presence of a pad was significantly (P < 0.05) associated with age, and several shoe variable (size, presence of a special shoe, overall wear matched) were significantly (P < 0.05) associated with sex. CLINICAL RELEVANCE: Except for variables related to special shoes, wear, and weight, 1 shoe for the respective fore- or hind limbs could be used as an indicator for the contralateral shoe worn by Thoroughbred racehorses without substantial loss of information. However, 1 shoe could not be used as an indicator for shoe characteristics of all 4 limbs. Some shoe characteristics are associated with age and sex, and these variables should be considered possible confounders in studies of shoe characteristics.

Animals↗

PubMed1996

Horseshoe characteristics as possible risk factors for fatal musculoskeletal injury of thoroughbred racehorses.

OBJECTIVE: To evaluate selected shoe characteristics as risk factors for fatal musculoskeletal injury (FMI) and specifically for suspensory apparatus failure (SAF) and cannon bone condylar fracture (CDY) of Thoroughbred racehorses in California. DESIGN: Case-control study. ANIMALS: Thoroughbred racehorses (n = 201) that died of were euthanatized at California racetracks between August 1992 and July 1994. PROCEDURE: Shoe characteristics were compared between case horses affected by FMI (155), SAF (79), and CDY (41) and control horses that died for reasons unrelated to the appendicular musculoskeletal system (non-FMI; 46). Multivariable logistic regression was used to estimate odds ratios for FMI, SAF, and CDY. RESULTS: Toe grabs were identified as possible risk factors for FMI, SAF, and CDY. The odds of FMI, SAF, and CDY were 1.8, 6.5, and 7.0, respectively, times greater for horses shod with low toe grabs than for horses shod without toe grabs on front shoes. Horses shod with regular toe grabs on front shoes had odds 3.5, 15.6, and 17.1 times greater (P < 0.05) for FMI, SAF, and CDY, respectively, compared with horses shod without toe grabs. The odds of horses shod with rim shoes were a third (P < 0.05) of those shod without rim shoes for either FMI or SAF. The apparent association between toe grab type and CDY may, in part, be attributable to concurrent SAF and CDY injuries in many horses. CLINICAL RELEVANCE: Avoiding the use of toe grabs should decrease the incidence of FMI, especially SAF, in Thoroughbred racehorses. The use of rim shoes that are more consistent with natural hoof shape may decrease injury risk.

Animals↗

PubMed1995

Independent mediation of unconditioned motor behavior by striatal D1 and D2 receptors in rats depleted of dopamine as neonates.

The effects of systemic administration of DA receptor antagonists suggest that unconditioned motor behavior in rats depleted of DA as neonates continues to be dependent upon dopaminergic transmission, yet the specific contribution of D1 and D2 receptors to these behaviors has been altered. The purpose of the present study was to determine whether these depletion-induced receptor changes are occurring at the level of striatal DA terminals and their targets. The ability of bilateral intrastriatal injections (0.5 microliter) of DA receptor antagonists to induce motoric deficits was determined in adult rats treated with vehicle or 6-OHDA (100 micrograms, intraventricular) on postnatal day 3. Administration of the D1-like antagonist SCH 23390 (0.5-2.0 micrograms) or the D2-like antagonist clebopride (1.0-4.0 micrograms) induced dose-dependent akinesia, catalepsy, and somatosensory neglect in vehicle-treated controls. In contrast, neither antagonist produced deficits in rats depleted of forebrain DA as neonates. However, combined administration of SCH 23390 + clebopride induced similar akinesia, catalepsy, and somatosensory neglect in both controls and DA depleted animals. Animals depleted of DA were more sensitive than controls to the low doses of this combined D1 + D2 antagonism. These results demonstrate that activation of striatal DA receptors remains necessary for unconditioned motor behavior in rats depleted of DA as neonates. However, the specific contributions of D1- and D2-like receptors to these behaviors differ between intact animals and those depleted of DA as neonates. The ability of endogenous DA acting at either D1 or D2 receptors to support spontaneous motor behavior in rats depleted of DA as neonates may contribute to their relative sparing from parkinsonian deficits.

Animals↗

PubMed1995

Dopaminergic modulation of striatal acetylcholine release in rats depleted of dopamine as neonates.

A repeated sessions, in vivo microdialysis design was used to determine the D1- and D2-like receptor modulation of striatal ACh efflux in intact adult rats and those depleted of DA on postnatal Day 3. Systemic administration of the D1-like agonist SKF 38393 (1.0 or 10.0 mg/kg, or the D2-like antagonist clebopride (1.0 or 10.0 mg/kg) increased ACh efflux in both controls and DA-depleted animals. Systemic administration of the D1-like antagonist SCH 23390 (0.05 or 0.2 mg/kg) or D2-like agonist quinpirole (0.5 or 1.0 mg/kg) decreased ACh efflux in both groups of animals. DA-depleted animals exhibited a larger response than did controls to the lower doses of these drugs. Intrastriatal administration of clebopride (10 microM) increased ACh efflux in DA-depleted animals. Finally, basal and clebopride-stimulated ACh efflux were unaffected by the repeated microdialysis sessions. These data demonstrate that the reciprocal modulation of striatal ACh efflux, seen in controls and in rats depleted of DA as adults, is also present in adults depleted of DA as neonates. Because the roles of D1- and D2-receptors in the expression of motor behavior differ between rats depleted of DA as adults vs as neonates, these data suggest that alterations in the dopaminergic modulation of striatal ACh release do not underlie the sparing from motoric deficits seen in animals depleted of DA as neonates.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗