Sheldon Lee Cooper - Academia.edu (original) (raw)

Papers by Sheldon Lee Cooper

The Journal of Immunology

A protein which binds to the Fc region of IgG has been isolated from the murine leukemia L1210. T... more A protein which binds to the Fc region of IgG has been isolated from the murine leukemia L1210. The isolation technique involves surface cross-linking of the cell's Fc receptors with the use of aggregated human IgG and anti-human IgG. This results in the redistribution (patch formation and capping) of the cell's Fc receptors. Lactoperoxidase-catalyzed radioiodination of the cells before complex binding indicates that Fc receptor redistribution results in the selective release of surface proteins. SDS-PAGE analyses of the supernatants from cells thus treated reveals a major peak corresponding to a molecular weight of 45,000 daltons. This protein has been purified from the cell supernatants by immunoprecipitation and chromatography of the percipitates on Sephadex G-200 under dissociating conditions. After separation from the immune complex this protein can be bound to heat-aggregated IgG, but not aggregated F(ab′)2 fragments. The 45,000 dalton protein appears to be the Fc rece...

Proceedings of the Nutrition Society, 2010

Malnutrition is common among acute hospital admissions, affecting up to 40 % of patients, with ma... more Malnutrition is common among acute hospital admissions, affecting up to 40 % of patients, with many deteriorating (78 %). MUST is NICE endorsed to aid identification of those at nutritional risk, validated against patient outcome in order to prevent the complications of malnutrition, and consequently reduce mortality, morbidity and cost to the health services. Liver disease patients are at particular risk of malnutrition. Lean weight loss can be masked by ascites or oedema, thus not revealing risk by use of MUST which relies, in part, upon change in weight. We recruited patients undergoing liver transplant assessment at the Queen Elizabeth Hospital Liver Unit, University Hospital Birmingham. MUST was calculated, and anthropometrics and DEXA scans were performed. An adjustment was made to MUST, by addition of one point for each of the following: fluid overload (significant ascites or oedema), chronic clinically evident encephalopathy, clinical jaundice and diarrhoea/steatorrhoea, creating the Malnutrition Liver Universal Screening Tool score (MLUST). Spearman's test was used to identify the degree of correlation between MUST and MLUST with anthropometrics and fat mass by DEXA scan. The degree of agreement between MUST and MLUST, with identification of malnutrition by mid-arm muscle circumference (MAMC) was calculated with the kappa statistic. Eighty nine patients with liver disease (52 male, median age 52.5, interquartile range 45.25-58) were examined. MUST and MLUST scores showed no correlation with tricep skin-fold thickness and hand-grip strength, and only MUST showed correlation with mid-arm circumference (r =-0.26, P = 0.038). However, both MUST and MLUST showed correlations with identification of being malnourished (including degree of malnourishment) by MAMC r = 0.25, P = 0.024 and r = 0.25, P = 0.022, respectively. MUST score showed a significant correlation with thigh region fat mass at DEXA (r =-0.33, P = 0.014), but not with arms or whole body; MLUST showed no correlation with DEXA. When MUST and MLUST were dichotomised into triggering referral or not, and agreement with identification of being malnourished by MAMC, MUST derived a kappa statistic of 0.16 (slight agreement) and MLUST 0.21 (fair agreement). Both MUST and MLUST correlate with anthropometrics to a similar degree. However, the agreement between identification of malnourished liver patients, in this select group of individuals, by MUST and MAMC is only slight, and marginally better with fair agreement with MLUST. This study illustrates that liver disease patients are difficult to screen for malnutrition, and we must be cognisant of factors that may hinder MUST such as those factors used in MLUST, a potentially useful screening tool that requires validation against outcome.

Introduction Methods Results Objectives References Current Status • Rheumatoid arthritis (RA) is ... more Introduction Methods Results Objectives References Current Status • Rheumatoid arthritis (RA) is a chronic multi-system autoimmune disease characterized by inflammatory synovitis. • Autoantibodies, such as anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), are important serological markers that distinguish RA from other forms of inflammatory arthritis; yet many patients with RA do not have measurable ACPA or RF. • IgG4 is the second most abundant isotype of ACPA and RF, after IgG1; but, it is not detected by diagnostic assays typically available. • Patients deemed " sero-negative " by standard assays may actually have high titers of the IgG4-specific isotype of ACPA and RF[1]. • In a combined effort from 2 large medical centers, UMASS Memorial & UVM, over 100 subjects have been recruited, of whom data and sera have been collected. • IgG1-and IgG4-specific ACPA & RF testing is being performed by Dr. Mercedes Rincon at University of Vermont Medical Cent...

Infection and Immunity, 1998

A common concern with many autoimmune diseases of unknown etiology is the extent to which tissue ... more A common concern with many autoimmune diseases of unknown etiology is the extent to which tissue T-lymphocyte infiltrates, versus a nonspecific infiltrate, reflect a response to the causative agent. Lyme arthritis can histologically resemble rheumatoid synovitis, particularly the prominent infiltration by T lymphocytes. This has raised speculation about whether Lyme synovitis represents an ongoing response to the causative spirochete, Borrelia burgdorferi , or rather a self-perpetuating autoimmune reaction. In an effort to answer this question, the present study examined the repertoire of infiltrating T cells in synovial fluid from nine Lyme arthritis patients, before and after stimulation with B. burgdorferi . Using a highly sensitive and consistent quantitative PCR technique, a comparison of the T-cell antigen receptor (TCR) β-chain variable (Vβ) repertoires of the peripheral blood and synovial fluid showed a statistically significant increase in expression of Vβ2 and Vβ6 in the l...

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1981

The repair-deficient mutant, mei-9 a in Drosophila melanogaster was investigated regarding its ef... more The repair-deficient mutant, mei-9 a in Drosophila melanogaster was investigated regarding its effect on spontaneous and X-ray-induced chromosome loss in male postmeiotic cells. From matings of males carrying a mei-9 a or an ordinary ring-X and a doubly marked Y chromosome (BSyy ÷) with mei-9 ~ or ordinary females, the spontaneous frequencies of complete loss, partial loss, and inferred ring-X loss (based on shifts in sex ratio female:male) were significantly higher with rnei-9 ~ than with non-mei-9 a. When males were given 3000 rad X-irradiation, frequencies of induced partial loss, inferred ring-X loss and the reduction in the number of progeny per female were significantly greater with mei-9 a than with non-mei-9 ~. The results provide evidence that the mei-9 ~ is a potentiator of both spontaneous and X-ray-induced chromosome lesions in sperm of the Drosophila male. Evidence is presented which implicates the presence of mei-9 ~ in the P1 female and not the male as (at least) largely responsible for the characteristic mei-9 ~ effects. The repair-deficient mutant, mei-9", an allele of mei-9, was originally selected as a female meiotic mutant [1,2]. It was subsequently shown that mei-9a-bearing cells do not remove UV-induced endonuclease-sensitive sites from DNA [4], and fail to show normal levels of repair replication following UVand X-irradiation as determined by CsC1 isopycnic centrifugation [11]. In addition, mei-9a-bearing larvae were hypersensitive to killing by nitrogen mustard, 2-acetylaminofluorene, and methyl methanesulfonate (MMS) [4], as well as by gamma-rays and UV [ 11 ], suggesting that the functional endonuclease(s) must be capable of recognizing a number of different DNA lesions. The ability of

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1981

Physiology & Behavior, 1987

Neuropharmacology, 1983

Both naloxone (3 and 10 mg X kg-1) and naltrexone (1-10 mg X kg-1) abolished the preference for a... more Both naloxone (3 and 10 mg X kg-1) and naltrexone (1-10 mg X kg-1) abolished the preference for a highly palatable 0.05% sodium saccharin solution in rats that had been adapted to a 22 hr water-deprivation schedule. The effect occurred as a result of a selective decrease in the consumption of the saccharin solution, since the intake of water, which was concurrently available in the two-fluid choice test, remained unaffected. When a less preferred saccharin solution was used (0.01%), naltrexone exerted a similar suppressant effect on the sodium preference, whilst naloxone failed to produce significant effects on the intake of saccharin solution or water. The data for the opiate agonists were interpreted in terms of a drug-induced blockade of the natural reward of highly palatable fluids in thirsty rats. In the same choice test, morphine and a stabilised enkephalin analogue, with a selective agonist action at mu-opiate receptors (RX783030), failed to influence the preference for the palatable saccharin solutions. In water-deprived animals, at least, exogenous opiate agonists, active at mu-receptors, did not appear to influence the reward of the palatable solutions.

Science, 1972

The first gamma-2 (γ 2) heavy chain disease protein Gif has pyrrolidinecarboxylic acid as its ami... more The first gamma-2 (γ 2) heavy chain disease protein Gif has pyrrolidinecarboxylic acid as its amino terminal residue, much of the Fd variable region, and an internal deletion of the heavy chain of about 100 residues corresponding to most of the Fd constant region. Normal sequence resumes with a glutamic acid residue at position 216 in the hinge region. This is the third gamma heavy chain disease protein where normal sequence resumes at the same position after the deletion.

Journal of Experimental Medicine

ABSTRACT

Oral Surgery, Oral Medicine, Oral Pathology, 1978

MEDICAL COLLEGE OF VIRGINIA AND GEORGETOWN UNIVERSITY An evaluation of the analgesic effects of p... more MEDICAL COLLEGE OF VIRGINIA AND GEORGETOWN UNIVERSITY An evaluation of the analgesic effects of preoperatively administered ibuprofen on postoperative pain after the surgical removal of impacted third molars was undertaken in 100 patients in a double-blind parallel treatment trial. The pretreatment with ibuprofen delayed the mean time of onset of postoperative pain more than 100 minutes, as compared to pretreatment with placebo. The severity of pain initially experienced postoperatively was less in the pretreated group. There was no detectable interaction between the pretreatment and the analgesics administered postoperatively. The results of this study suggest that it is possible to delay the onset and lessen the severity of postoperative pain by preoperative administration of a nonsteroidal, antiinflammatory analgesic, such as ibuprofen.

Journal of Crohn's & colitis, Jan 13, 2015

United European gastroenterology journal, 2014

Oesophageal adenocarcinoma (OAC) incidence is rising rapidly and prognosis remains poor. Endoscop... more Oesophageal adenocarcinoma (OAC) incidence is rising rapidly and prognosis remains poor. Endoscopic surveillance of Barrett's oesophagus (BO) remains controversial. A nested case-control study was undertaken to evaluate risk factors for progression of BO to OAC, potentially guiding surveillance efforts. The Health Improvement Network database includes general practitioner consultations from 5 million UK subjects. BO subjects with 1-year minimum of follow up were followed until development of OAC or end of time on database. Demographic variables (age, gender, smoking, body mass index) and data on medication considered negatively (aspirin/nonsteroidal anti-inflammatory drugs/proton pump inhibitors) or positively associated (lower oesophageal sphincter-relaxing and asthma drugs) with OAC development were studied. Cox regression analysis-derived hazard ratios with 95% confidence intervals estimated the relative risk for OAC progression. A total of 3749 BO subjects were studied: 55 d...

Behavioral and Neural Biology, 1986

Saline-treated and amphetamine-treated (7 mg/kg, ip, immediate) male rats from a Spragne-Dawley s... more Saline-treated and amphetamine-treated (7 mg/kg, ip, immediate) male rats from a Spragne-Dawley substrain were observed in two test environments designed to elicit different investigative responses in normal rats. Snout contact with the substrate was generated by placing the rat in a small enclosed cage. Absence of snout contact was induced by placement of the rat on a square elevated platform. Detailed ethological records were kept of locomotion, rearing, sitting, grooming, gnawing, and sleeping throughout the 90-min session. Amphetamine-treated rats incorporated environmentally contingent bodily postures into their forms of stereotyped behavior. The postures were characteristic of those evinced initially by the saline-treated rats in the same test environment. The control rats showed appropriate changes in their investigative behavior when the apparatus was changed at l0 and at 30 min postinjection. The amphetamine-treated rats, however, were completely unresponsive to such changes at 30 min and only partially so at 10 rain postinjection. It was concluded that there is a temporal gradient of decreasing readiness to modify repetitive behavior after a single, large dose of amphetamine.

Physiology & Behavior, 1986

ABSTRACT Apomorphine (0.01 to 5 mg/kg, SC) was administered to male rats observed singly in the o... more ABSTRACT Apomorphine (0.01 to 5 mg/kg, SC) was administered to male rats observed singly in the open-field. The behavior of each rat was coded using a microprocessor during 3 preinjection and 9 postinjection trials of 6 min duration over a 2 hr session. The behavior categories included grooming, yawning, turning, nodding and gnawing, as well as snout contact and nonsnout contact variants of locomoting, rearing and sitting. Dose-dependent increases in the time spent in snout contact with the field surface were noted throughout the complete dose range. Both the peak and duration of the snout contact epoch increased with the dose of apomorphine. The integrated time spent in all types of snout contact proved to be the best behavioral measure for discriminating between doses of apomorphine even though the topography of snout contact response changed as a function of the dose.

The Journal of Immunology

A protein which binds to the Fc region of IgG has been isolated from the murine leukemia L1210. T... more A protein which binds to the Fc region of IgG has been isolated from the murine leukemia L1210. The isolation technique involves surface cross-linking of the cell's Fc receptors with the use of aggregated human IgG and anti-human IgG. This results in the redistribution (patch formation and capping) of the cell's Fc receptors. Lactoperoxidase-catalyzed radioiodination of the cells before complex binding indicates that Fc receptor redistribution results in the selective release of surface proteins. SDS-PAGE analyses of the supernatants from cells thus treated reveals a major peak corresponding to a molecular weight of 45,000 daltons. This protein has been purified from the cell supernatants by immunoprecipitation and chromatography of the percipitates on Sephadex G-200 under dissociating conditions. After separation from the immune complex this protein can be bound to heat-aggregated IgG, but not aggregated F(ab′)2 fragments. The 45,000 dalton protein appears to be the Fc rece...

Proceedings of the Nutrition Society, 2010

Malnutrition is common among acute hospital admissions, affecting up to 40 % of patients, with ma... more Malnutrition is common among acute hospital admissions, affecting up to 40 % of patients, with many deteriorating (78 %). MUST is NICE endorsed to aid identification of those at nutritional risk, validated against patient outcome in order to prevent the complications of malnutrition, and consequently reduce mortality, morbidity and cost to the health services. Liver disease patients are at particular risk of malnutrition. Lean weight loss can be masked by ascites or oedema, thus not revealing risk by use of MUST which relies, in part, upon change in weight. We recruited patients undergoing liver transplant assessment at the Queen Elizabeth Hospital Liver Unit, University Hospital Birmingham. MUST was calculated, and anthropometrics and DEXA scans were performed. An adjustment was made to MUST, by addition of one point for each of the following: fluid overload (significant ascites or oedema), chronic clinically evident encephalopathy, clinical jaundice and diarrhoea/steatorrhoea, creating the Malnutrition Liver Universal Screening Tool score (MLUST). Spearman's test was used to identify the degree of correlation between MUST and MLUST with anthropometrics and fat mass by DEXA scan. The degree of agreement between MUST and MLUST, with identification of malnutrition by mid-arm muscle circumference (MAMC) was calculated with the kappa statistic. Eighty nine patients with liver disease (52 male, median age 52.5, interquartile range 45.25-58) were examined. MUST and MLUST scores showed no correlation with tricep skin-fold thickness and hand-grip strength, and only MUST showed correlation with mid-arm circumference (r =-0.26, P = 0.038). However, both MUST and MLUST showed correlations with identification of being malnourished (including degree of malnourishment) by MAMC r = 0.25, P = 0.024 and r = 0.25, P = 0.022, respectively. MUST score showed a significant correlation with thigh region fat mass at DEXA (r =-0.33, P = 0.014), but not with arms or whole body; MLUST showed no correlation with DEXA. When MUST and MLUST were dichotomised into triggering referral or not, and agreement with identification of being malnourished by MAMC, MUST derived a kappa statistic of 0.16 (slight agreement) and MLUST 0.21 (fair agreement). Both MUST and MLUST correlate with anthropometrics to a similar degree. However, the agreement between identification of malnourished liver patients, in this select group of individuals, by MUST and MAMC is only slight, and marginally better with fair agreement with MLUST. This study illustrates that liver disease patients are difficult to screen for malnutrition, and we must be cognisant of factors that may hinder MUST such as those factors used in MLUST, a potentially useful screening tool that requires validation against outcome.

Introduction Methods Results Objectives References Current Status • Rheumatoid arthritis (RA) is ... more Introduction Methods Results Objectives References Current Status • Rheumatoid arthritis (RA) is a chronic multi-system autoimmune disease characterized by inflammatory synovitis. • Autoantibodies, such as anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), are important serological markers that distinguish RA from other forms of inflammatory arthritis; yet many patients with RA do not have measurable ACPA or RF. • IgG4 is the second most abundant isotype of ACPA and RF, after IgG1; but, it is not detected by diagnostic assays typically available. • Patients deemed " sero-negative " by standard assays may actually have high titers of the IgG4-specific isotype of ACPA and RF[1]. • In a combined effort from 2 large medical centers, UMASS Memorial & UVM, over 100 subjects have been recruited, of whom data and sera have been collected. • IgG1-and IgG4-specific ACPA & RF testing is being performed by Dr. Mercedes Rincon at University of Vermont Medical Cent...

Infection and Immunity, 1998

A common concern with many autoimmune diseases of unknown etiology is the extent to which tissue ... more A common concern with many autoimmune diseases of unknown etiology is the extent to which tissue T-lymphocyte infiltrates, versus a nonspecific infiltrate, reflect a response to the causative agent. Lyme arthritis can histologically resemble rheumatoid synovitis, particularly the prominent infiltration by T lymphocytes. This has raised speculation about whether Lyme synovitis represents an ongoing response to the causative spirochete, Borrelia burgdorferi , or rather a self-perpetuating autoimmune reaction. In an effort to answer this question, the present study examined the repertoire of infiltrating T cells in synovial fluid from nine Lyme arthritis patients, before and after stimulation with B. burgdorferi . Using a highly sensitive and consistent quantitative PCR technique, a comparison of the T-cell antigen receptor (TCR) β-chain variable (Vβ) repertoires of the peripheral blood and synovial fluid showed a statistically significant increase in expression of Vβ2 and Vβ6 in the l...

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1981

The repair-deficient mutant, mei-9 a in Drosophila melanogaster was investigated regarding its ef... more The repair-deficient mutant, mei-9 a in Drosophila melanogaster was investigated regarding its effect on spontaneous and X-ray-induced chromosome loss in male postmeiotic cells. From matings of males carrying a mei-9 a or an ordinary ring-X and a doubly marked Y chromosome (BSyy ÷) with mei-9 ~ or ordinary females, the spontaneous frequencies of complete loss, partial loss, and inferred ring-X loss (based on shifts in sex ratio female:male) were significantly higher with rnei-9 ~ than with non-mei-9 a. When males were given 3000 rad X-irradiation, frequencies of induced partial loss, inferred ring-X loss and the reduction in the number of progeny per female were significantly greater with mei-9 a than with non-mei-9 ~. The results provide evidence that the mei-9 ~ is a potentiator of both spontaneous and X-ray-induced chromosome lesions in sperm of the Drosophila male. Evidence is presented which implicates the presence of mei-9 ~ in the P1 female and not the male as (at least) largely responsible for the characteristic mei-9 ~ effects. The repair-deficient mutant, mei-9", an allele of mei-9, was originally selected as a female meiotic mutant [1,2]. It was subsequently shown that mei-9a-bearing cells do not remove UV-induced endonuclease-sensitive sites from DNA [4], and fail to show normal levels of repair replication following UVand X-irradiation as determined by CsC1 isopycnic centrifugation [11]. In addition, mei-9a-bearing larvae were hypersensitive to killing by nitrogen mustard, 2-acetylaminofluorene, and methyl methanesulfonate (MMS) [4], as well as by gamma-rays and UV [ 11 ], suggesting that the functional endonuclease(s) must be capable of recognizing a number of different DNA lesions. The ability of

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1981

Physiology & Behavior, 1987

Neuropharmacology, 1983

Both naloxone (3 and 10 mg X kg-1) and naltrexone (1-10 mg X kg-1) abolished the preference for a... more Both naloxone (3 and 10 mg X kg-1) and naltrexone (1-10 mg X kg-1) abolished the preference for a highly palatable 0.05% sodium saccharin solution in rats that had been adapted to a 22 hr water-deprivation schedule. The effect occurred as a result of a selective decrease in the consumption of the saccharin solution, since the intake of water, which was concurrently available in the two-fluid choice test, remained unaffected. When a less preferred saccharin solution was used (0.01%), naltrexone exerted a similar suppressant effect on the sodium preference, whilst naloxone failed to produce significant effects on the intake of saccharin solution or water. The data for the opiate agonists were interpreted in terms of a drug-induced blockade of the natural reward of highly palatable fluids in thirsty rats. In the same choice test, morphine and a stabilised enkephalin analogue, with a selective agonist action at mu-opiate receptors (RX783030), failed to influence the preference for the palatable saccharin solutions. In water-deprived animals, at least, exogenous opiate agonists, active at mu-receptors, did not appear to influence the reward of the palatable solutions.

Science, 1972

The first gamma-2 (γ 2) heavy chain disease protein Gif has pyrrolidinecarboxylic acid as its ami... more The first gamma-2 (γ 2) heavy chain disease protein Gif has pyrrolidinecarboxylic acid as its amino terminal residue, much of the Fd variable region, and an internal deletion of the heavy chain of about 100 residues corresponding to most of the Fd constant region. Normal sequence resumes with a glutamic acid residue at position 216 in the hinge region. This is the third gamma heavy chain disease protein where normal sequence resumes at the same position after the deletion.

Journal of Experimental Medicine

ABSTRACT

Oral Surgery, Oral Medicine, Oral Pathology, 1978

MEDICAL COLLEGE OF VIRGINIA AND GEORGETOWN UNIVERSITY An evaluation of the analgesic effects of p... more MEDICAL COLLEGE OF VIRGINIA AND GEORGETOWN UNIVERSITY An evaluation of the analgesic effects of preoperatively administered ibuprofen on postoperative pain after the surgical removal of impacted third molars was undertaken in 100 patients in a double-blind parallel treatment trial. The pretreatment with ibuprofen delayed the mean time of onset of postoperative pain more than 100 minutes, as compared to pretreatment with placebo. The severity of pain initially experienced postoperatively was less in the pretreated group. There was no detectable interaction between the pretreatment and the analgesics administered postoperatively. The results of this study suggest that it is possible to delay the onset and lessen the severity of postoperative pain by preoperative administration of a nonsteroidal, antiinflammatory analgesic, such as ibuprofen.

Journal of Crohn's & colitis, Jan 13, 2015

United European gastroenterology journal, 2014

Oesophageal adenocarcinoma (OAC) incidence is rising rapidly and prognosis remains poor. Endoscop... more Oesophageal adenocarcinoma (OAC) incidence is rising rapidly and prognosis remains poor. Endoscopic surveillance of Barrett's oesophagus (BO) remains controversial. A nested case-control study was undertaken to evaluate risk factors for progression of BO to OAC, potentially guiding surveillance efforts. The Health Improvement Network database includes general practitioner consultations from 5 million UK subjects. BO subjects with 1-year minimum of follow up were followed until development of OAC or end of time on database. Demographic variables (age, gender, smoking, body mass index) and data on medication considered negatively (aspirin/nonsteroidal anti-inflammatory drugs/proton pump inhibitors) or positively associated (lower oesophageal sphincter-relaxing and asthma drugs) with OAC development were studied. Cox regression analysis-derived hazard ratios with 95% confidence intervals estimated the relative risk for OAC progression. A total of 3749 BO subjects were studied: 55 d...

Behavioral and Neural Biology, 1986

Saline-treated and amphetamine-treated (7 mg/kg, ip, immediate) male rats from a Spragne-Dawley s... more Saline-treated and amphetamine-treated (7 mg/kg, ip, immediate) male rats from a Spragne-Dawley substrain were observed in two test environments designed to elicit different investigative responses in normal rats. Snout contact with the substrate was generated by placing the rat in a small enclosed cage. Absence of snout contact was induced by placement of the rat on a square elevated platform. Detailed ethological records were kept of locomotion, rearing, sitting, grooming, gnawing, and sleeping throughout the 90-min session. Amphetamine-treated rats incorporated environmentally contingent bodily postures into their forms of stereotyped behavior. The postures were characteristic of those evinced initially by the saline-treated rats in the same test environment. The control rats showed appropriate changes in their investigative behavior when the apparatus was changed at l0 and at 30 min postinjection. The amphetamine-treated rats, however, were completely unresponsive to such changes at 30 min and only partially so at 10 rain postinjection. It was concluded that there is a temporal gradient of decreasing readiness to modify repetitive behavior after a single, large dose of amphetamine.

Physiology & Behavior, 1986

ABSTRACT Apomorphine (0.01 to 5 mg/kg, SC) was administered to male rats observed singly in the o... more ABSTRACT Apomorphine (0.01 to 5 mg/kg, SC) was administered to male rats observed singly in the open-field. The behavior of each rat was coded using a microprocessor during 3 preinjection and 9 postinjection trials of 6 min duration over a 2 hr session. The behavior categories included grooming, yawning, turning, nodding and gnawing, as well as snout contact and nonsnout contact variants of locomoting, rearing and sitting. Dose-dependent increases in the time spent in snout contact with the field surface were noted throughout the complete dose range. Both the peak and duration of the snout contact epoch increased with the dose of apomorphine. The integrated time spent in all types of snout contact proved to be the best behavioral measure for discriminating between doses of apomorphine even though the topography of snout contact response changed as a function of the dose.