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Biomedical subjects

M E Hamilton

Publications and source records attributed to M E Hamilton.

At least 19 recordsLinked to original sources
PubMed2001

Effects of forebrain microinjection of cholecystokinin on dopamine cell firing rate.

In anesthetized rats, midbrain dopamine (DA) neuronal firing rate was differentially sensitive to focal brain microinjection of cholecystokinin peptides (CCK-4 and CCK-8) and N-methyl-D-aspartate (NMDA) into nucleus accumbens, amygdala and prefrontal cortex. Whereas changes in DA neuronal firing rate were frequently observed in response to intra-amygdalar microinjection of CCK peptides, NMDA was most effective in eliciting changes in DA neuronal activity following intra-accumbal microinjection. Thus, stimulation of amygdalar CCK receptors and accumbal excitatory amino acid receptors may participate in the afferent regulation of midbrain DA neuronal function.

Amino Acids↗
PubMed2000

Overflow of dopamine and cholecystokinin in rat nucleus accumbens in response to acute drug administration.

Cholecystokinin octapeptide (CCK-8) coexists with dopamine (DA) in rat mesencephalic neurons that project to the nucleus accumbens. To obtain indices of corelease, microdialysis probes were placed in the posterior nucleus accumbens of anesthetized rats, which were then injected acutely (s.c.) with drugs that exert known effects on DA neuronal function. Microdialysis samples were assayed for DA and CCK-8 to determine the differential overflow of these cotransmitters in response to drug treatment. Haloperidol (0.5 mg/kg), d-amphetamine (1 mg/kg), and TCP (5 mg/kg) preferentially increased DA overflow, whereas morphine (5 mg/kg) elicited marked increases in the overflow of both DA and CCK-8. These results suggest that the release of accumbal DA and CCK-8 can be differentially regulated by drug treatment.

Animals↗
PubMed1999

Mutation of putative phosphorylation sites in the 5-hydroxytryptamine3 receptor does not eliminate its modulation by ethanol.

The function of the 5-hydroxytryptamine3 (5-HT3) receptor is enhanced by ethanol, but the amino acid residue(s) that confers sensitivity to ethanol remains to be identified. Phosphorylation of the related GABA(A) receptor has been implicated in conferring its sensitivity to ethanol. In common with the GABA(A) receptor, the 5-HT3 receptor contains multiple consensus sites for protein kinases. To evaluate the possibility that phosphorylation of the 5-HT3 receptor underlies its ethanol sensitivity, we examined the ability of ethanol to enhance 5-HT-mediated currents in a mutant 5-HT3 receptor containing no intracellular serines, threonines, or tyrosines. Mutation of these 13 residues in the intracellular loops produced a modest leftward shift in the 5-HT concentration response curve, with the EC50's for 5-HT decreasing from 0.839 +/- 0.03 microM in the wild-type receptor to 0.713 +/- 0.03 microM in the mutant receptor. Cooperativity of the 5-HT binding sites was enhanced by the mutations, with Hill coefficients of 2.92 for the wild-type receptor and 3.74 for the mutant receptor, respectively. In oocytes expressing mutant receptors, ethanol (50 to 200 mM) enhanced the currents produced by low concentrations of 5-HT by approximately 5 to 45%, which was not statistically different from the potentiation produced by ethanol in wild-type receptors. These results suggest that ethanol enhancement of the 5-HT3 receptor function does not require receptor phosphorylation.

Animals↗
PubMed1998

Money as a tool to extinguish conditioned responses to cocaine in addicts.

Classical conditioning principles offer a nondrug way to treat cocaine dependence. Eleven male subjects with the primary diagnosis of cocaine dependence were placed into one of two groups. The experimental group was asked to handle $500 cash in a mock budgetary task. The control group was asked to just imagine handling and budgeting the money. The subjects rated their craving-related feelings before and after each task. The experimental group showed significantly more craving after the money-handling task as compared to the control group, and the scores improved with time and as more tasks were completed. These data show that craving induced by handling cash is powerful and can be attenuated, at least on a short-term basis, using classical extinction procedures.

Analysis of Variance↗
PubMed1995

Effects of administration of cholecystokinin into the VTA on DA overflow in nucleus accumbens and amygdala of freely moving rats.

The carboxyterminal octapeptide of cholecystokinin (CCK-8) coexists with dopamine (DA) in mesolimbic neurons of the ventral tegmental area (VTA). In the present study, in vivo microdialysis in freely moving rats was used to assess the relative effects of sulfated CCK-8 (CCK-8S), unsulfated CCK-8 (CCK-8US) and CCK tetrapeptide (CCK-4), focally injected into the VTA, on DA overflow in two mesolimbic DA/CCK-8S terminal regions, the nucleus accumbens and the amygdala. Consistent with electrophysiological findings, microinjection of CCK-8S, but not CCK-8US or CCK-4, elicited increases in DA overflow in both terminal regions. In the absence of anatomical evidence of CCK-containing fibers in the VTA region, it seems reasonable to conclude that the modulation of terminal DA overflow by CCK-8S through actions at the somatodendritic region represents a form of autoregulation of these cells. Whereas CCK-8US and CCK-4 are preferential CCK-B receptor agonists, CCK-8S binds non-selectively to CCK-A and CCK-B receptors. Thus, these results implicate CCK-A receptors in the stimulatory effects of CCK-8S on VTA DA neurons.

Amygdala↗
PubMed1992

Striatal extracellular dopamine in conscious vs. anesthetized rats: effects of chloral hydrate anesthetic on responses to drugs of different classes.

Many investigations using the microdialysis technique have been performed in anesthetized animals, both in this laboratory and elsewhere. Concern arises with this preparation that the anesthetic may compromise neuronal function, or that it may interact with test drugs affecting neurotransmitter overflow. In addition, in these studies the microdialysis probe typically is introduced into the brain on the day of testing, and data collection commences within an hour or two following probe insertion. It has been suggested that transmitter recovered in the perfusate probably represents leakage due to tissue damage as well as exocytotic release, and may not accurately reflect neuronal responses to the manipulations of interest. Such potential confounds present important implications for the interpretation of data from these studies. The present investigation examined the effects of chloral hydrate anesthetic on (1) basal dopamine (DA) overflow in the anterior striatum, and (2) DA responses to systemically delivered drugs of two different classes known to influence DA activity. Three putative indices of impulse-dependent release were measured: (a) the time course and stability of basal DA overflow over several hours; (b) sodium channel involvement by adding tetrodotoxin (TTX) to the artificial CSF; and (c) calcium channel involvement using magnesium (Mg) in a calcium-free perfusate. Basal DA levels became stable in both conscious and anesthetized preparations by the second hour after probe insertion. Levels of recovered DA overflow in the anterior striata of conscious rats were approximately double those in chloral hydrate-anesthetized rats. Consistent with other findings, this suggests a general depression of CNS function by chloral hydrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Oral health knowledge and habits of senior elementary school students.

Despite improvements in children's dental health, and significant resource allocation to health education programs, few recent studies have investigated the associations of oral health knowledge, behaviors, and status. This study of 11-year-old children (N = 6,329) in northeastern Ontario used a supervised self-complete questionnaire and a clinical examination to gather baseline data on, and test associations of, caries and periodontal knowledge, self-reported oral health behaviors and source of knowledge, and oral health status. Results show the children had poor knowledge of caries preventive measures such as water fluoridation, dental sealants, and choice of snack foods. Periodontal knowledge was better, but children confused plaque and calculus. Respondents claimed good oral health habits, with 73 percent claiming to brush at least twice daily, 88 percent claiming to use toothpaste, 42 percent claim to floss at least twice weekly, and 84 percent claiming an annual dental visit. Children with the best knowledge claimed dentist and school as the sources. High knowledge was associated with good oral health habits (P less than .001) and low DMFT score (P less than .001). Good habits were not related to DMFT score (P = .1095). Logistic regression showed high knowledge was associated with English cultural status, urban school area, good habits, having a dental sealant, and attending a fluoride-rinse school (P less than .05). Findings suggest a need to reinforce caries preventive teaching, to investigate the effect of cultural status, dental experience, and residence status on oral health knowledge, and to further test the efficacy of different oral health education programs delivered by different sources.

Analysis of Variance↗
PubMed1991

Eosinophilic fasciitis associated with L-tryptophan ingestion.

A 62 year old woman taking L-tryptophan developed eosinophilic fasciitis shortly after starting an exercise class. She received prednisone without benefit but improved after azathioprine treatment was started and L-tryptophan was discontinued. As products containing L-tryptophan have recently been implicated in development of the eosinophilia-myalgia syndrome it is suggested that the use of L-tryptophan might have contributed to the development of eosinophilic fasciitis in this patient. Similarities with toxic oil syndrome are noted. Additional studies are warranted to determine the prevalence of L-tryptophan ingestion among patients diagnosed as having eosinophilic fasciitis.

Arm↗
PubMed1988

Feeding elicited by dynorphin (1-13) microinjections into the ventral tegmental area in rats.

Both the endogenous opioid peptide, dynorphin (1-13) (DYN), and morphine elicited dose-dependent feeding when microinjected into the ventral tegmental area of food-satiated rats. DYN was 50,000 times more potent than morphine in producing feeding. Whereas the ED50 for morphine was in the nanomole range, the ED50 for DYN was in the femtomole range. Administration of a narcotic antagonist attenuated DYN-elicited feeding. These data suggest a possible role for DYN in the VTA in opioid modulation of feeding behavior.

Animals↗
PubMed1986

Influence of p-chloroamphetamine and methysergide on the escape deficits provoked by inescapable shock.

The effects of serotonergic manipulations on the escape interference engendered by exposure to inescapable shock were assessed. Consistent with the view that the behavioral interference was related to reductions of serotonin (5-HT), treatment with the 5-HT receptor blocker methysergide mimicked the effects of inescapable shock in that it increased escape latencies. Conversely, acute treatment with a moderate dose of the 5-HT releasing agent p-chloroamphetamine (PCA) effectively antagonized the escape interference ordinarily provoked by inescapable shock. The effects of PCA were behaviorally distinguishable from the previously observed effects of catecholamine stimulants. Whereas catecholamine stimulants applied prior to either inescapable shock or escape testing eliminated the interference, PCA antagonized the behavioral disruption only if it was administered before testing. It is suggested that catecholamine alterations may be fundamental in the provocation of the interference, whereas 5-HT variations may contribute to the expression of the behavioral disturbance.

Amphetamines↗
PubMed1981

Age influences the clinical and serologic expression of systemic lupus erythematosus.

The clinical and serologic characteristics of 17 patients with onset of systemic lupus erythematosus (SLE) after age 50 were compared with those of 49 younger patients. All patients were followed prospectively for a mean duration of 47 months. A clinical and serological data base was established for each patient, and information collected at each visit to a lupus clinic was analyzed by computer. The clinical featured distinguishing old-age SLE were a low incidence of significant renal disease and prominent pleuropericarditis and arthritis throughout the period of followup. Serologic abnormalities were milder in older patients. Thus, hypocomplementemia, anti-DNA antibodies, and C1q precipitins occurred less frequently, and rheumatoid factor was more often present than in younger patients with SLE. Regression analysis suggested linear change in disease expression with age rather than distinct age-related subgroups.

Adult↗