Biomedical subjects

E O'Hare

Publications and source records attributed to E O'Hare.

At least 19 recordsLinked to original sources

PubMed2006

An operant determination of the behavioral mechanism of benzodiazepine enhancement of food intake.

RATIONALE: A recent review paper by Cooper (Appetite 44:133-150, 2005) has pointed out that a role for benzodiazepines as appetite stimulants has been largely overlooked. Cooper's review cited several studies that suggested the putative mechanism of enhancement of food intake after benzodiazepine administration might involve increasing the perceived pleasantness of food (palatability). OBJECTIVES: The present study examined the behavioral mechanism of increased food intake after benzodiazepine administration. MATERIALS AND METHODS: The cyclic-ratio operant schedule has been proposed as a useful behavioral assay for differentiating palatability from regulatory effects on food intake (Ettinger and Staddon, Physiol Behav 29:455-458, 1982 and Behav Neurosci 97:639-653, 1983). The current study employed the cyclic-ratio schedule to determine whether the effects on food intake of chlordiazepoxide (CDP) (5.0 mg/kg), sodium pentobarbital (5.0 mg/kg), and picrotoxin (1.0 mg/kg) were mediated through palatability or regulatory processes. RESULTS: The results of this study show that both the benzodiazepine CDP and the barbiturate sodium pentobarbital increased food intake in a manner similar to increasing the palatability of the ingestant, and picrotoxin decreased food intake in a manner similar to decreasing the palatability of the ingestant. CONCLUSIONS: These results suggest that the food intake enhancement properties of benzodiazepines are mediated through a mechanism affecting perceived palatability.

Animals↗

PubMed2005

Granisetron attenuates exercise-induced conditioned taste aversion in the rat.

A conditioned taste aversion (CTA) paradigm was used in the present study to investigate whether CTA produced by exercise could be attenuated by the 5-HT(3) receptor antagonist granisetron. Male Sprague-Dawley rats were randomly allocated to one of four groups (Ns=6) and were exposed to salty (0.128 M sodium chloride) or sour (0.00138M citric acid) solutions. Subjects were injected with either saline solution (1.0 ml, 0.9%) or granisetron (0.5mg/kg, IP) and were exposed to 30 min of forced wheel running exercise (70 revolutions/30min) 10 min after injection. Exercise induced CTA to both the salty (3.7 ml intake) and sour-flaroured (3.1ml intake) solutions as compared with no exercise (intake 14.0 and 13.7 ml), and administration of granisetron significantly attenuated the exercise-induced CTA to the salty- and sour-flavoured solutions.

Animals↗

PubMed2005

Parenteral antioxidant treatment preserves temporal discrimination following intrahippocampal aggregated Abeta(1-42) injections.

There is evidence that oxidative stress may play a role in the neuropathology of Alzheimer's disease (AD). This study used an aggregated beta-amyloid (Abeta) injection model of AD in the rat, and a recycling conjunctive schedule of food reinforcement to examine the effects of bilateral intrahippocampal injections of aggregated Abeta(1-42) (5.0 microl/side) on temporal discrimination, and the efficacy of the antioxidant alpha-tocopherol (150 mg/kg daily p.o.) in alleviating these effects. The results indicated that bilateral intrahippocampal injections of aggregated Abeta(1-42) detrimentally affected temporal discrimination from five-day block 31-35 post-injections until the end of the study (90 days post-injections). Daily treatment with alpha-tocopherol improved temporal discrimination under the recycling conjunctive schedule following aggregated Abeta(1-42) injections from the five-day block 61-65 days until the end of the study.

Amyloid beta-Peptides↗

PubMed2005

Chronic intracerebroventricular infusion of lipopolysaccharide: effects of ibuprofen treatment and behavioural and histopathological correlates.

Twenty male Wistar rats were trained under an alternating-lever cyclic-ratio (ALCR) schedule of food reinforcement. When responding showed no trends, each subject was subcutaneously implanted with an Alzet osmotic mini-pump, connected to a chronic indwelling cannula extending into the lateral ventricle of the brain. The mini-pumps were primed to infuse 0.25 microl lipopolysaccharide (LPS) (1.0 microg/0.25 ml) or 0.25 microl artificial cerebrospinal fluid (aCSF) per hour and were implanted for 28 days. LPS infusion produced behavioural deficits which chronic ibuprofen treatment (40 mg/kg every 12 h) alleviated. Infusion of LPS induced R 1282-positive amyloid deposits, and activation of microglia and astrocytes. Ibuprofen treatment reduced the numbers of activated microglia, and withdrawal of ibuprofen resulted in an increase in activated microglia; however, ibuprofen treatment had no effect on numbers of activated astrocytes in the LPS-infused subjects.

Amyloid beta-Peptides↗

PubMed2004

Behavioral and neurochemical mechanisms of the action of mild stress in the enhancement of feeding.

Rats were trained to respond under a cyclic-ratio schedule of reinforcement composed of an ascending, followed by a descending, sequence of ratio values. Subjects were trained while exposed to 70 dB white noise, then tested while exposed to 70 or 90 dB white noise. Exposure to 90 dB white noise elevated the response function (p<.02). Naloxone was then administered intraperitoneally at 0.3. 1.0. and 3.0 mg/kg under 70 dB and 90 dB white noise. Naloxone administration (1.0 and 3.0 mg/kg) significantly depressed the response function obtained under 90 dB white noise (ps<.01) but did not affect the function obtained under 70 dB white noise. These findings suggest that mild stress increases food intake through a mechanism affecting palatability enhanced by the release of endogenous opioids.

Acoustic Stimulation↗

PubMed2002

Behavioural and histopathological analyses of ibuprofen treatment on the effect of aggregated Abeta(1-42) injections in the rat.

It has been suggested that inflammatory processes may play a role in the development of Alzheimer's disease (AD), and that nonsteroidal anti-inflammatory drug treatments may provide protection against the onset of AD. In the current study male Wistar rats were trained in two-lever operant chambers under an alternating lever cyclic-ratio ratio (ALCR) schedule. When responding showed no trends, subjects were divided into groups. One group was bilaterally injected into the CA3 area of the hippocampus with 5 microl of aggregated beta-amyloid (Abeta) suspension, and one group was bilaterally injected into the CA3 area of the hippocampus with 5 microl of sterile saline. Subgroups were treated twice daily with 0.1 ml (40 mg/kg) ibuprofen administered orally. The results indicated that chronic administration of ibuprofen protected against detrimental behavioural effects following aggregated Abeta injections. Withdrawal of ibuprofen treatment from aggregated Abeta-injected subjects produced a decline in behavioural performance to the level of the non-treated aggregated Abeta-injected group. Ibuprofen treatment reduced the numbers of reactive astrocytes following aggregated Abeta injection, and withdrawal of ibuprofen resulted in an increase of reactive astrocytes. These results suggest that induced inflammatory processes may play a role in AD, and that ibuprofen treatment may protect against some of the symptoms seen in AD.

Alzheimer Disease↗

PubMed2001

Identification of central sites involved in butorphanol-induced feeding in rats.

Butorphanol (BT), a mixed kappa- and mu-opioid receptor agonist, induces vigorous food intake in rats. Peripheral injection of BT seems to increase food intake more effectively than intracerebroventricular administration. To further elucidate the nature of BT's influence on consummatory behavior, we examined which feeding-related brain areas exhibit increased c-Fos immunoreactivity (IR) following subcutaneous injection of 4 mg/kg body weight BT, a dose known to induce a maximal orexigenic response. We also evaluated whether direct administration of BT into the forebrain regions activated by peripheral BT injection affects food intake. Peripheral BT administration induced c-Fos-IR in the hypothalamic paraventricular nucleus (PVN), central nucleus of the amygdala (CeA), and nucleus of the solitary tract (NTS). However, 0.1-30 microg BT infused into the CeA, failed to increase food intake 1, 2, and 4 h after injection. Only the highest dose of BT (30 microg) injected into the PVN increased feeding. These results suggest that the PVN, CeA, and NTS mediate the effects of peripherally-injected BT. The PVN or CeA are probably not the main target sites of immediate BT action.

Amygdala↗

PubMed2000

ARC POMC mRNA and PVN alpha-MSH are lower in obese relative to lean zucker rats.

Effects of obesity on gene expression for opioid peptides and neuropeptide-Y (NPY) in the arcuate nucleus (ARC), and on opioid peptides and alpha-melanocyte stimulating hormone (alpha-MSH) in the paraventricular nucleus (PVN) were examined in obese Zucker rats (18 weeks old). Obese Zucker rats are insulin-resistant, diabetic and hyperleptinemic as indicated by high serum glucose, insulin and leptin levels. ARC proOpiomelanocortin (POMC) mRNA levels were significantly lower in the obese relative to lean Zucker rats and ARC proNeuropeptide Y (proNPY) mRNA levels were higher (P<0.05). There were no differences in proDynorphin and proEnkephalin mRNA levels in the ARC (0.05). Obese Zucker rats had lower alpha-MSH and dynorphin A(1-17) peptide levels in the paraventricular nucleus (PVN) (P<0.05), but did not have lower PVN beta-endorphin peptide levels (0.05). The decrease in POMC in the ARC and decrease in alpha-MSH in the PVN seen in the obese Zucker rat in the present study suggest that reduced activity of the melanocortin system in the ARC to PVN pathway may contribute to the related hyperphagia. Reduced activity of the melanocortin system in the ARC to PVN pathway may be due to a disturbance of leptin signaling coupling to POMC.

Animals↗

PubMed2000

Varied duration of congenital hypothyroidism potentiates perseveration in a response alternation discrimination task.

The behavior of five groups of rats (seven rats per group) made hypothyroid for varying lengths of time and one group of seven normal control rats was assessed under forced alternation fixed-ratio (FR1, FR3, FR5 and FR10), alternating lever cyclic-ratio (ALCR) and progressive-ratio (PR3) schedules of reinforcement. Hypothyroidism was produced by adding methimazole (MMI) to the drinking water of pregnant dams from embryonic day E16 to postnatal day P25. Four groups were given replacement thyroxine (T4) injections beginning at specific time points (P1, P7, P13, and P19). There were no differences in behavioral performance between control and experimental groups under the FR schedule, which indicates that the animals' sensorimotor abilities were intact. Under the forced ALCR schedule, all groups reached criteria similarly. However, under the choice lever ALCR schedule, control animals and those which received T4 replacement from early on (P1, P7, P13 groups) performed well and all had reached criteria by 11 sessions. In contrast, animals which did not receive any T4 replacement or received it late (P19 group) took longer to reach criteria and 5/14 animals had not reached criteria at all by 20 sessions. This deterioration in performance was paralleled by an increase in perseverative behavior as evidenced by an increased frequency of pressing the wrong lever when alternation of lever was required. This suggests that congenital hypothyroidism results in increased perseveration leading to a decrease in learning when a discrimination between correct and incorrect operanda is made available.

Animals↗

PubMed2000

Maternal depression and parenting behavior: a meta-analytic review.

The results of 46 observational studies were analyzed to assess the strength of the association between depression and parenting behavior and to identify variables that moderated the effects. The association between depression and parenting was manifest most strongly for negative maternal behavior and was evident to a somewhat lesser degree in disengagement from the child. The association between depression and positive maternal behavior was relatively weak, albeit significant. Effects for negative maternal behavior were moderated by timing of the depression: Current depression was associated with the largest effects. However, residual effects of prior depression were apparent for all behaviors. Socioeconomic status, child age, and methodological variables moderated the effects for positive behavior: Effects were strongest for studies of disadvantaged women and mothers of infants. Studies using diagnostic interviews and self-report measures yielded similar effects, suggesting that deficits are not specific to depressive disorder. Research is needed to identify factors that affect the magnitude of parenting deficits among women who are experiencing depression and other psychological difficulties.

Adult↗

PubMed1999

Congenital hypothyroidism impairs response alternation discrimination behavior.

The behavior of six congenitally hypothyroid and six normal control rats was assessed under forced alternation fixed-ratio, alternating lever cyclic-ratio (ALCR) and progressive-ratio schedules of reinforcement. Hypothyroidism was produced by adding methimazole (MMI) to the drinking water of pregnant dams from embryonic day 16 to postnatal day 25. There were no differences in behavioral performance between MMI-treated and control animals under the fixed-ratio and progressive ratio schedules. There were also no differences in circulating triiodothyronine levels between groups at the end of the study. Under the ALCR schedule, when alternation of responding was forced during the first three cycles but both levers (choice) were presented during the last three cycles (correct lever active), the entire control group reached a competency criteria in nine sessions. In contrast, only two MMI-treated animals reached criteria after 17 sessions, and the remaining four MMI-treated animals did not reach criteria by 30 sessions of training. These results suggest that congenital hypothyroidism impairs learning when a discrimination between correct and incorrect operanda is made available.

Animals↗

PubMed1999

Discriminative stimulus effects of morphine: central versus peripheral training.

While it is well known that rats can discriminate a peripheral injection of morphine from a saline injection, to our knowledge no one has trained rats to discriminate a direct brain-site injection of morphine from saline. In the present series of studies, one group of rats was trained to discriminate morphine (0.3 microgram) from saline injected into the perifornical area of the hypothalamus (PFA), a process that took rats about 37 sessions to learn. A dose response generalization curve for PFA-injected morphine (0.01, 0.03, 0.1, and 0.17 microgram) was generated in which the two highest doses of morphine generalized to the morphine-appropriate training stimulus. Intraperitoneal (i.p.) injection of 3 mg/kg, but not 1 mg/kg morphine, resulted in morphine-appropriate responding in the PFA morphine-trained rats. A second group of rats was trained to discriminate i.p. injections of 3 mg/kg morphine from injections of saline. A dose-response generalization test for i.p.-injected morphine (0.3, 0.56, 1.0, and 1.7 mg/kg) was conducted in which the 0.17 mg/kg dose of morphine generalized to the morphine-appropriate training stimulus. Generalization tests using PFA-injected morphine doses (0.17, 0.56, 1.0, and 3.0 microgram) failed to result in morphine-appropriate responding in the i.p. morphine-trained rats. Naloxone administered into the PFA (50 microgram) or the periphery (3 mg/kg, i.p.) blocked morphine discrimination in the PFA-trained rats. However, when naloxone was injected into the PFA (50 microgram) together with i.p. morphine (3 mg/kg) in animals trained using i.p. injections, the antagonist failed to block morphine-appropriate responding. Thus, while peripheral injection of morphine generalized to the discriminative stimulus effects of morphine produced under PFA-injection training, the opposite effects were not noted.

Analgesics, Opioid↗

PubMed1999

Delayed behavioral effects following intrahippocampal injection of aggregated A beta (1-42).

Beta amyloid protein (A beta) is the major extracellular component of Alzheimer's disease (AD) plaques. In the current study, A beta (1-42) was aggregated in vitro using a method which produces A beta aggregates similar to those found in the AD brain. Twelve male Sprague-Dawley rats were trained in two-lever operant chambers under an alternating lever cyclic-ratio (ALCR) schedule. When performance was stable on the ALCR schedule, six subjects were injected (bilaterally into the CA3 area of the dorsal hippocampus) with 5.0 microliters aggregated A beta in suspension, and the remaining six subjects were injected with 5.0 microliters sterile water. Behavioral testing resumed 5 days after surgery and continued for 90 days post-injection. Aggregated A beta injection did not affect the number of lever switching errors made in a daily session but did affect the number of incorrect lever response perseverations. After approximately 30 days post-injection, aggregated A beta injection detrimentally affected ability to track the changing parameters of the schedule, and decreased the efficiency by which subjects obtained reinforcers. From approximately day 50 post-injection onward, A beta-injected subjects demonstrated significantly higher numbers of incorrect lever response perseverations than did sterile water-injected subjects. These effects appeared to be central rather than peripheral, as A beta injection did not decrease running response rates under the ALCR schedule. The delayed onset of behavioral effects seen in this and other behavioral studies may be a result of a cascade of potentially harmful responses induced through glial activation following aggregated A beta injection.

Amyloid beta-Peptides↗

PubMed1999

The effect of naloxone on food-motivated behavior in the obese Zucker rat.

We assessed differences in food reinforced behavior between obese and lean Zucker rats with a progressive ratio schedule 3 (PR3) in which a subject emitted three additional lever-presses each time a reinforcer was delivered. The number of responses required for a reinforcer eventually exceeded its value, termed the "break point", a sensitive measure of food motivated behavior. Break points were higher in obese rats than lean controls for grain pellets (27.5 versus 9.5, P = 0.01) but not for sweet pellets (51.6 versus 38.5, P = 0.31). We determined if naloxone (0.01-3.0 mg/kg, SC), which reduces free food intake in obese Zucker rats, affects food motivated behavior in obese Zuckers and lean controls. Naloxone reduced break points in both obese and lean rats to a similar extent when working for either grain pellets or sweet pellets. Under free-access feeding conditions, naloxone again decreased pellet intake similarly in the obese and lean Zucker rats. Naloxone appeared to decrease free-access pellet consumption to a greater extent than break point in both groups. These results show that (1) obese rats exhibit higher levels of performance for food than lean rats only when working for the less valued grain pellet, (2) naloxone reduces both break points and free-access pellet consumption independent of genotype, and (3) naloxone appears to decrease food more effectively in rats given free access to food than in rats working for food.

Animals↗

PubMed1999

Effects of neuropeptide Y on the discriminative stimulus and antinociceptive properties of morphine.

Previous research indicates that opioid receptor blockade diminishes the effects of neuropeptide Y (NPY) on feeding and memory. Conversely, NPY attenuates naloxone-precipitated morphine withdrawal. The present study evaluated the effects of NPY on the discriminative stimulus and antinociceptive effects produced by the prototypical mu opioid, morphine. Rats were trained to discriminate 5.6 mg/kg morphine (IP) from saline using a standard two-lever, food-reinforced, drug discrimination procedure. Across a range of doses (3.0, 5.0, and 10 microg), intracerebroventricular (ICV) injection of NPY failed to substitute for, antagonize, or potentiate the discriminative stimulus effects of morphine. A warm-water tail-withdrawal procedure was used to examine the antinociceptive effects of morphine and NPY, alone and in combination. NPY (3.0 and 10 microg, ICV) failed to alter tail-withdrawal latencies from 52 degrees and 56 degrees C water, whereas morphine (1.0-30 mg/kg, IP) produced a dose-related increase in latencies at both water temperatures. A 10-microg dose of NPY also failed to alter the antinociceptive effects of morphine. This study does not support the idea that the discriminative stimulus and antinociceptive effects of morphine are dependent on an NPYergic pathway.

Analgesics, Opioid↗

PubMed1998

Fibrillar beta-amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivo.

To determine the stability of beta-amyloid peptide (Abeta) and the glial and neuronal changes induced by Abeta in the CNS in vivo, we made single injections of fibrillar Abeta (fAbeta), soluble Abeta (sAbeta), or vehicle into the rat striatum. Injected fAbeta is stable in vivo for at least 30 d after injection, whereas sAbeta is primarily cleared within 1 d. After injection of fAbeta, microglia phagocytize fAbeta aggregates, whereas nearby astrocytes form a virtual wall between fAbeta-containing microglia and the surrounding neuropil. Similar glial changes are not observed after sAbeta injection. Microglia and astrocytes near the injected fAbeta show a significant increase in inducible nitric oxide synthase (iNOS) expression compared with that seen with sAbeta or vehicle injection. Injection of fAbeta but not sAbeta or vehicle induces a significant loss of parvalbumin- and neuronal nitric oxide synthase-immunoreactive neurons, whereas the number of calbindin-immunoreactive neurons remains unchanged. These data demonstrate that fAbeta is remarkably stable in the CNS in vivo and suggest that fAbeta neurotoxicity is mediated in large part by factors released from activated microglia and astrocytes, as opposed to direct interaction between Abeta fibrils and neurons.

Amyloid beta-Peptides↗

PubMed1998

Intrahypothalamic discriminative stimulus effects of neuropeptide Y.

Neuropeptide Y (NPY) is one of the most ubiquitous neurotransmitters in the CNS and has been implicated in a variety of psychological and physiological functions. The current study investigated whether intrahypothalamic (I.H.) administrations of NPY were behaviorally discriminable from saline injections. Rats were trained to differentially respond based on whether they received I.H. injections of NPY (0.5 microg/0.5 microl) or saline (0.5 microl 0.9% NaCl). Subjects demonstrated discriminative control (85% correct in 8 out of 10 consecutive sessions) after a mean of 32 sessions. The ability of subjects to discriminate I.H. NPY from saline was dose dependent, with the lowest NPY dose tested (0.03 microg/0.5 microl) generalizing to saline. The opioid antagonist naloxone blocked the discrimination of NPY when administered I.P. (3.0 mg/kg) or I.H. (50 microg/0.5 microl).

Animals↗

PubMed1997

Serum anticholinergic activity and behavior following atropine sulfate administration in the rat.

Anticholinergic agents such as atropine and scopolamine have long been suggested to produce delirium-like states in humans and experimental animals. Evidence for an anticholinergic mechanism in the pathogenesis of human delirium has accumulated, leading to studies of the behavioral effects of the anticholinergic drug atropine in animals. The current study addresses the adequacy of animal models of delirium in terms of sensitivity, specificity and pharmacological relevance. A multiple fixed-ratio fixed-interval reinforcement schedule was used to test the effects of relatively low doses of atropine on behavior in rats. Additionally, total serum anticholinergic activity (SAA) was measured under dose and time course conditions identical to those used in the behavioral study. Atropine reduced high and low rates of responding in a dose-dependent manner, and SAA increased in a dose dependent manner. SAA at atropine doses of 0.1 mg/kg to 1.0 mg/kg was similar to that found in delirious humans. These behavioral and serum level data suggest that relatively low doses of atropine, substantially below those used in previous attempts to model delirium using rats, may be more pharmacologically relevant to delirium and may minimize non-specific peripheral effects of this drug.

Animals↗