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Biomedical subjects

P Winn

Publications and source records attributed to P Winn.

At least 19 recordsLinked to original sources
PubMed2004

An examination of d-amphetamine self-administration in pedunculopontine tegmental nucleus-lesioned rats.

The pedunculopontine tegmental nucleus (PPTg) has long been suggested to have a role in reward-related behaviour, and there is particular interest in its possible role in drug reward systems. Previous work found increased i.v. self-administration (IVSA) of d-amphetamine following PPTg lesions when training had included both operant pre-training and priming injections. The present study examined the effect of excitotoxin lesions of the PPTg on d-amphetamine IVSA under three training conditions. Naive: no previous experience of d-amphetamine or operant responding. Pre-trained: given operant training with food before lesion surgery took place. Primed: given single non-contingent d-amphetamine infusion (0.1 mg/0.l ml) at the start of each session. Rats in all conditions were given either ibotenate or phosphate buffer control lesions of the PPTg before d-amphetamine (0.1 mg/0.1 ml infusion) IVSA training took place. Rats received eight sessions of training under a fixed ratio (FR2) schedule of d-amphetamine IVSA, followed by four sessions under a progressive ratio (PR5) schedule. In the naive condition, PPTg-lesioned rats were attenuated in their responding under FR2, and took significantly fewer infusions under PR5 than the control group. Under FR2 in the pre-trained condition, there was no difference between PPTg excitotoxin and control lesioned rats; however, PPTg-lesioned rats took significantly fewer infusions under the PR5 schedule. In the primed condition, there were no differences between PPTg-lesioned and control rats under either FR2 or PR5 schedules. These data demonstrate that operant training prior to PPTg lesion surgery corrects some, but not all, of the deficits seen in the naive condition. PPTg-lesioned rats in both naive and pre-trained conditions showed reduced responding for d-amphetamine under a PR5 schedule. These deficits are overcome by priming with d-amphetamine. We suggest that alterations in striatal dopamine activity following PPTg lesions underlie these effects.

Analysis of Variance↗
PubMed2003

Behavioural sensitisation to repeated d-amphetamine: effects of excitotoxic lesions of the pedunculopontine tegmental nucleus.

The pedunculopontine tegmental nucleus (PPTg) interacts with anatomical systems thought to be involved in mediating sensitisation of the locomotor response to repeated d-amphetamine. The PPTg has direct and indirect connections with the nucleus accumbens and prefrontal cortex, and also influences midbrain dopamine activity through direct projections to substantia nigra and ventral tegmental area. In this experiment, the development of behavioural sensitisation to the locomotor stimulant effects of repeated d-amphetamine was examined in rats bearing excitotoxic lesions of the PPTg, and sham-lesioned controls. Rats were given repeated d-amphetamine (1.5 mg/kg i.p.) treatment in an on-off procedure, with saline and d-amphetamine given on alternate days, such that rats received a total of seven d-amphetamine and seven saline treatments. Locomotor responses were measured in photocell cages. On the first day of d-amphetamine treatment, there was no difference between excitotoxin and sham-lesioned rats. Development of sensitisation to the locomotor stimulant effects of d-amphetamine was delayed in PPTg-lesioned rats, relative to the sham-lesioned control rats. However, there was no difference between lesion and control groups in the locomotion seen on saline-treatment days. These data suggest that the PPTg is involved in the development of behavioural sensitisation to the locomotor stimulant effects of repeated d-amphetamine, and indicate that traditional striatal circuitry models of the mechanisms underlying sensitisation should be extended to include the PPTg.

Amphetamine↗
PubMed2002

The effect of excitotoxic lesions of the pedunculopontine tegmental nucleus on performance of a progressive ratio schedule of reinforcement.

The pedunculopontine tegmental nucleus has connections with sites in both dorsal and ventral striatum, and a number of studies have suggested that it has a role in reward-related behaviour. The present experiment aimed to investigate the perception of reward in pedunculopontine tegmental nucleus-lesioned rats responding for food under a progressive ratio schedule, which measures willingness to work for a given reward. Rats were trained on a progressive ratio-5 schedule for food reward, then given ibotenic acid or sham lesions of the pedunculopontine tegmental nucleus. Their performance under this schedule was examined again following recovery from surgery. Compared with sham-lesioned rats, those with lesions of the pedunculopontine tegmental nucleus showed significantly reduced breaking points and significantly longer post-reinforcement pauses. However, there was no difference between the groups in their latency to collect food pellets once earned, suggesting that pedunculopontine tegmental nucleus excitotoxin and sham-lesioned rats were equally motivated by the presence of food. Excitotoxin-lesioned rats made significantly more responses on the control lever and more entries to the food hopper as progressive ratio increment increased, but did not differ from controls when the schedule requirement was low. These results are interpreted as indicating no global loss of motivation, since lesioned rats performed normally at low schedule requirements, and were as fast as controls to collect pellets. But as the schedule requirement increased, excitotoxin-lesioned rats showed reductions in responding on the active lever (that is, a reduction in breaking point) and an increase in inappropriate responses towards the food hopper and the control lever.We consider these data to indicate that the behavioural deficits in pedunculopontine-lesioned rats arise not from a sensory or hedonic change, but from alteration in the control of motor output.

Animals↗
PubMed2002

Examination of the role of the pedunculopontine tegmental nucleus in radial maze tasks with or without a delay.

Two radial maze tasks, random foraging and delayed spatial win-shift, have been used to investigate, in rats, the functions and inter-relationships of structures connected through the corticostriatal loops, such as the prelimbic cortex, nucleus accumbens, ventral pallidum and mediodorsal thalamus. The random foraging task is designed to investigate animals' ability to use spatial information to guide foraging on-line. The delayed spatial win-shift task requires, in addition, that animals hold spatially relevant information in working memory across a delay period. The pedunculopontine tegmental nucleus receives direct output from ventral striatal systems and might therefore be expected to share functional properties with them. In the present experiments we have examined the performance of rats bearing bilateral excitotoxic lesions of the pedunculopontine tegmental nucleus on both of these tasks. In acquisition tests rats were given bilateral lesions before any training took place, while in retention tests appropriate training to predetermined criterion levels of performance took place before lesions were made. In both tasks, and in both acquisition (no prelesion training) and retention (prelesion training) tests, rats with pedunculopontine lesions made significantly more errors in selecting arms to enter than did control rats. There was no motor impairment present in pedunculopontine tegmental nucleus-lesioned rats - on the contrary, on measures of speed (latency to make first arm choice and the mean time for subsequent choices) pedunculopontine-lesioned rats were slightly faster than control rats. We suggest that the pedunculopontine tegmental nucleus shares functional properties with frontostriatal systems and that it forms part of a brainstem-directed stream of striatal outflow different to the cortical re-entrant system via the thalamus.

Animals↗
PubMed2001

Ventral mesopontine projections of the caudomedial shell of the nucleus accumbens and extended amygdala in the rat: double dissociation by organization and development.

The shell of the nucleus accumbens and central division of the extended amygdala are telencephalic structures that influence motor activity and lately have been regarded by some as components of a single functional-anatomic continuum. Each has a highly differentiated internal organization and output system and distinct pharmacologic responses however, and it is thus likely that each subserves distinct contributions to behavior. In this investigation, nucleus accumbens and extended amygdala outputs were compared by using retrograde tracing in adult and postnatal rats. Fluoro-Gold, when injected into the ventral tegmental area, produced substantial retrograde labeling in the adult nucleus accumbens shell, but only trivial amounts in the central division of the extended amygdala. Injection sites in the lateral mesopontine tegmentum produced robust labeling in the central extended amygdala but little in the nucleus accumbens. The projections of extended amygdala were substantially developed by postnatal day 1, whereas those of the caudomedial shell of the nucleus accumbens only reached the ventral tegmental area by approximately postnatal day 6. Few neurons projecting from the caudomedial shell of the accumbens to the ventral tegmental area were observed even at postnatal day 21. In consideration of the reported importance of the nucleus accumbens, particularly the caudomedial shell, in neural processing related to reward and motivation and the central nervous system response to antipsychotic drugs, it may be important to determine whether processes occurring during the protracted postnatal development of the caudomedial shell are vulnerable to destructive circumstances, such as drug intoxication, maternal separation, or social isolation.

Aging↗
PubMed2001

The effects of excitotoxic lesions of the pedunculopontine tegmental nucleus on conditioned place preference to 4%, 12% and 20% sucrose solutions.

A number of studies have suggested that the pedunculopontine tegmental nucleus (PPTg) may play a role in reward-related behaviour. The present study was intended to investigate this further using conditioned place preference. In conditioned place preference paradigms the amount of time spent in a preferred environment is proportional to the value of the reinforcement present, until a maximum is reached. In the present experiments we aimed to determine whether this relationship was affected by lesions of the PPTg by examining the formation of a conditioned place preference to either 4%, 12% or 20% sucrose solutions in food-deprived PPTg lesioned rats. The conditioned place preference apparatus had two compartments different in colour, smell and floor texture. During conditioning, rats were restricted to one compartment or the other, one of which was paired with sucrose. This was carried out during 30 min sessions, alternating conditioned or nonconditioned trials for 14 days. On the test day, rats were given access to both compartments through a connecting chamber, and were scored for side preference over 15 min. Both PPTg and sham lesioned rats showed a conditioned place preference to 12% and 20% sucrose, but no place preference was formed by either group to 4% sucrose. There was no significant difference between the groups in the place preference shown. Consumption of 4% sucrose was not affected by excitotoxic lesions of the PPTg, but PPTg lesioned rats consumed significantly more 12% and 20% sucrose than sham controls. This suggests that perception of reward value, as judged by CPP formation, is unchanged by excitotoxic lesions of the PPTg. The increased consumption of 12% and 20% sucrose shown by rats bearing such lesions is therefore not likely to be a product of altered reward perception.

Animals↗
PubMed2001

Update on nursing home care in Oklahoma.

In Oklahoma approximately 36,000 people live in a nursing home. This article reviews those initiatives by Medicare, the Health Care Finance Administration (HCFA), and the American Medical Directors' Association to improve the quality of care that physicians and nurses provide to residents in long-term care facilities, specifically nursing homes.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed2000

Medication administration hassles reported by family caregivers of dependent elderly persons.

BACKGROUND: Even under the new long-term care mantra for increased home- and community-based care options, attention to and an understanding of the ways that family caregivers are managing complex care for dependent elderly persons, for example, with medication administration, have been slow to materialize. METHODS: Twenty-three family caregivers completed semistructured, face-to-face interviews to capture the shared and idiosyncratic experiences of individuals responsible for all aspects of medication administration regimens for elderly, dependent family members. Data analysis consisted of content analysis of the verbatim interview transcripts. This article reports an emerging typology of caregiver medication administration hassles derived from the interviews. RESULTS: Based on 122 separate accounts, three categories of medication administration hassles were identified. The categories (with the percentage of all accounts represented by the category) include (i) scheduling logistics (29.5%), (ii) administration procedures (31.9%), and (iii) safety issues (38.6%). CONCLUSIONS: Primary care providers must continually reevaluate and simplify medication regimens for dependent elderly persons in the care of family members, and the family caregivers must be given adequate training and access to ongoing information support systems to help them perform safe and effective medication administration responsibilities.

Adult↗
PubMed1998

Excitotoxic lesions of the subthalamic nucleus ameliorate asymmetry induced by striatal dopamine depletion in the rat.

We investigated the effect of unilateral dorsal striatal dopamine depletion (by intrastriatal infusion of 6-OHDA), ibotenic acid lesions of the subthalamic nucleus (STN) and combined dopamine depletion and STN lesions on sensorimotor asymmetry using a test of somatosensory asymmetry [T. Schallert et al., Pharmacol. Biochem. Behav. 16 (1982) 455-462]. The unilateral striatal dopamine depletion resulted in a somatosensory asymmetry. This asymmetry was ameliorated in the rats with combined dopamine depletion and STN lesion. indicating the potential beneficial nature of STN inactivation in rats with striatal dopamine depletion.

Animals↗
PubMed1998

Frontal syndrome as a consequence of lesions in the pedunculopontine tegmental nucleus: a short theoretical review.

In this review, it is argued that the consequence of bilateral damage to the pedunculopontine tegmental nucleus (PPTg) in experimental animals is the production of a form of frontal syndrome. Frontal syndrome is a term used to describe the behavioural consequences of damage to the frontal lobes in human patients. These behavioural changes can be classified as disinhibition of behaviour (a release of behavioural control), the production of inappropriate behaviour (which in patients can be either inappropriate actions or verbal behaviour), and the production of perseverative behaviour (the maintenance of an action beyond the point at which it should have been terminated). The psychological changes which underlie these behavioural changes are thought to involve executive functions, which include such things as the prospective planning of sequences of actions, attentional shifting and working memory. In this review, I attempt to demonstrate two things: first, that there are significant anatomical connections from frontostriatal systems to the PPTg. The motor cortex projects directly to the PPTg while the prefrontal cortex contacts it via striatal circuitry, forming clear routes by which the frontal lobes can communicate with the PPTg. Second, having established the existence of connections between frontostriatal systems and the PPTg, behavioural data are described. Experimental animals bearing bilateral lesions of the PPTg have been examined in a wide variety of tasks. Animals bearing such lesions are not impaired in basic processes of feeding, drinking, locomotion, or grooming and simple observation of lesioned rats' normal behaviour reveals no obvious gross impairment in function. However, the results of more subtle tests reveal a wide variety of deficits in various tasks. The outcome of these experiments are in many ways contradictory, but in the vast majority of cases, the changes can be described as involving disinhibition of behaviour, the release of inappropriate behaviour, and the production of perseverative behaviour. Anatomical and behavioural data support the conclusion that there are functional connections between frontal systems and the PPTg. This review also discusses what psychological processes might be served by such connections.

Animals↗
PubMed1998

Long-lived picture priming in normal elderly persons and demented patients.

Normal elderly control participants showed short-term (10-min delay) and long-term (12 months delay) priming on the Gollin Figures Test. Nearly all patients with Alzheimer's disease or vascular dementia showed short-term priming, but the magnitude of their priming was less than that of controls. Significant long-term priming was not observed for the dementia groups. Differences between controls and dementia patients on the short-term priming test may depend upon structural-perceptual processes that are intact in dementia patients and controls and explicit memory functions available only to controls. The same model could account for differences between normal elderly and dementia patients on the long-term priming test, but several other explanations are also plausible.

Aged↗
PubMed1997

Neurotoxicity, blood-brain barrier breakdown, demyelination and remyelination associated with NMDA-induced lesions of the rat lateral hypothalamus.

Excitotoxins have been widely used to make lesions in the brains of experimental animals because they have the ability to destroy neurones while sparing fibres of passage. Because loss of fibres of passage can confound the interpretation of lesion effects, this property is of considerable value. Recently, however, there have been reports indicating that excitotoxins acting at different sites within the rat CNS not only destroy neurones but also strip myelin from fibres and compromise the integrity of the blood-brain barrier. However, some reports also indicate that the myelin content of the lesioned area recovers. Excitotoxic lesions of the lateral hypothalamus have been shown to produce local demyelination. The present studies sought to investigate this effect further by (1) defining the time course of demyelination and possible remyelination after excitotoxic lesions of the lateral hypothalamus made with N-methyl-D-aspartate (NMDA); (2) establishing the relationships between neuronal loss, de- and remyelination after various doses of NMDA; and (3) examining the integrity of the blood-brain barrier using an immunohistochemical probe. Our data show that after injection of NMDA into the lateral hypothalamus there was neuronal loss, blood-brain barrier disruption (followed by recovery over approximately 12 days), triggering of reactive gliosis, invasion of the lesioned area by cells from outwith the CNS, demyelination over an area coexistent with but not exceeding the area of neuronal loss, and remyelination. Remyelination occurred over a period of 3 months following the production of the lesion and was associated initially with blood vessels. It occurred across the whole of the lesioned area, not by encroachment from the borders. All doses of NMDA that produced neuronal death also produced demyelination. These data confirm that excitotoxic lesions of the lateral hypothalamus demyelinate fibres, but show for the first time that remyelination occurs here. They are consistent with reports concerning excitotoxin actions at other CNS sites and indicate that de- and remyelination after excitotoxic lesions is a ubiquitous process. Consideration should be given to this when using excitotoxins to make fibre-sparing lesions.

Animals↗
PubMed1997

Expression of game-related and generic knowledge by dementia patients who retain skill at playing dominoes.

Patients with dementia who remain skilled at musical performance or playing bridge fail explicit memory tests for information related to their skills, suggesting that implicit memory mediates their preserved skills. To reexamine this issue, 23 dementia patients and 15 elderly controls of comparable domino-playing skill were compared on tests of naming, verbal fluency, and domino knowledge. On an explicit test of domino knowledge, the patients scored well below the elderly controls, performing no better than students who were unfamiliar with the game. But when game-like situations were created with real dominoes, both the skilled controls and the patients with dementia chose optimal moves and verbally explained their choices equally well. On naming and fluency tests, the skilled patients showed no advantage over patients of comparable dementia severity who had no retained skill. In dementia, some complex knowledge seems intact but is accessible only in particular contexts.

Aged↗
PubMed1997

On the relationships between the striatum and the pedunculopontine tegmental nucleus.

In this essay we consider the role of the pedunculopontine tegmental nucleus as a striatal output station. We review the relevant anatomical, electrophysiological, behavioral, and pathological studies and conclude that the pedunculopontine tegmental nucleus occupies an important position in striatal outflow, receiving motor output from the dorsal striatum and information from the ventral striatum relating to limbic processes of motivation and reinforcement. The hypothesis we present is that the pedunculopontine tegmental nucleus is at the very least an integral component of the limbic-motor interface, although in discussing this concept we also assess the likelihood that the limbic-motor interface is in fact a distributed system-that is, that limbic-motor interfacing is not all done by a single structure in the central nervous system but that different aspects of it are served by different systems. We present the hypothesis that the pedunculopontine tegmental nucleus is one critical site through which limbic information concerned with motivation, reinforcement, and the construction of novel associations can gain access to a stream of motor outflow coming from the caudate-putamen and directed toward pontomedullary systems without reference back to the cerebral cortex. This hypothesis is important because it highlights striatal outflow, which is not processed through the cortical re-entry systems, and also emphasizes the importance of pontine systems in cognitive processing.

Caudate Nucleus↗
PubMed1996

Modulation of dopamine efflux in the nucleus accumbens after cholinergic stimulation of the ventral tegmental area in intact, pedunculopontine tegmental nucleus-lesioned, and laterodorsal tegmental nucleus-lesioned rats.

Microinjections of the cholinergic receptor agonist nicotine and the cholinesterase inhibitor neostigmine were made into the ventral tegmental area (VTA) of urethane-anesthetized rats, and dopamine (DA) efflux in the nucleus accumbens was measured using in vivo chronoamperometry. Dose-dependent increases in the chronoamperometric signals corresponding to increased DA efflux were observed in the nucleus accumbens of normal intact rats after cholinergic stimulation of the VTA. The source of the cholinergic input to the VTA was investigated by making excitotoxic lesions in either the laterodorsal tegmental nucleus (LDTg) or the pedunculopontine tegmental nucleus (PPTg). Compared with sham-operated control animals, which showed the same response as intact, nonlesioned rats, ibotenate lesions of the LDTg attenuated the stimulatory effects of intra-VTA neostigmine on DA efflux in the nucleus accumbens. In contrast, rats with ibotenate lesions of the PPTg showed normal nucleus accumbens DA eflux after intra-VTA injections of neostigmine. Such lesions in the PPTg attenuate DA efflux in the caudate-putamen stimulated by injections of neostigmine into the substantia nigra pars compacta (SNc). The present data show that cholinergic neurons in the LDTg, but not the PPTg, regulate the activity of DA-containing neurons in the VTA, which complements previous data showing that cholinergic neurons in the PPTg regulate DA-containing neurons in the SNc.

Animals↗
PubMed1996

Schedule-induced polydipsia and the nucleus accumbens: electrochemical measurements of dopamine efflux and effects of excitotoxic lesions in the core.

The efflux of dopamine (DA) in the nucleus accumbens (NAcc) core during the acquisition of schedule-induced polydipsia (drinking in response to intermittent food presentation) was measured using rapid scan voltammetry. DA efflux increased throughout the SIP sessions, always reaching a peak after the session had terminated. There was, however, no relationship between the acquisition of the drinking response to intermittent food presentation and DA efflux. When water was absent from the test chamber, DA efflux still increased and reached a peak after food delivery was terminated, dissociating drinking and increased DA efflux. Taken in conjunction with previously presented data, these results suggest that the presence of DA in the NAcc core might be necessary for the development of SIP but that its efflux does not bear a systematic relationship to the acquisition of adjunctive behaviour. In a second experiment the effects of NMDA-induced lesions of the NAcc core on the acquisition and performance of SIP were examined. Lesioned rats did not differ to controls in terms of water intake, mean drinking bout length, latency to panel press for food or to begin drinking. The number of drinking bouts/min was reduced in lesioned rats, but did not reach statistical significance; the number of panel presses/min was significantly reduced in lesioned rats. These data demonstrate that the NAcc core is not necessary for the development of SIP but that elements of performance are affected. This suggests that the development of SIP can be fractionated and that different neural elements control different aspects of its expression. These data are used to support the hypothesis that the NAcc core is involved in focusing behaviour and regulating switching between response options.

Animals↗