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G D Phillips

Publications and source records attributed to G D Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1997

Enhanced acquisition of discriminative approach following intra-amygdala d-amphetamine.

This study examined the role of the mesoamygdaloid dopamine projection in stimulus-reward learning. Bilateral post-session intra-amygdala microinjections of d-amphetamine were carried out in rats during training in a discriminative approach task known to be sensitive to experimental manipulations of the amygdala. The experiment consisted of two phases: discriminative approach training, and a subsequent assessment of instrumental conditioned reward efficacy. During discriminative approach training, subjects were trained to associate a neutral stimulus with 10% w/v sucrose reward. Each trial consisted of a 1-s light stimulus followed by a 5-s presentation of the sucrose reward. Approach behaviour into the recess housing sucrose reward was measured during each trial. Inappropriate approach behaviour (approach outside of the trial periods) was punished by delaying the next trial. Intra-amygdala d-amphetamine (10 microg/side) enhanced the rate of acquisition of discriminative approach behaviour. This effect was most evident early during training (sessions 2-4) and by the tenth session both groups had reached similar asymptotic performance. Horizontal and vertical activity increased slightly across sessions, but there was no indication of a differential effect of d-amphetamine. Thus, intra-amygdala microinjections of d-amphetamine enhanced selectively the acquisition of the stimulus-reward association. During a subsequent test of instrumental conditioned reward, presentation of the conditioned light stimulus was made contingent upon performance of a novel lever-pressing response (probability 0.5). Responding on a second, control lever was without programmed consequences. Sucrose reward was not available at any point, and subjects were tested drug-free. In both groups the conditioned stimulus was found to possess significant conditioned rewarding efficacy. Extraneous behaviour was increased in the d-amphetamine group but the rewarding properties of the conditioned stimulus were unaltered. These findings demonstrate that the mesoamygdaloid dopamine projection modulates the acquisition of a stimulus-reward association, but is apparently without subsequent effect on the rewarding efficacy of a conditioned stimulus.

Amphetamine↗
PubMed1997

Repeated d-amphetamine enhances stimulated mesoamygdaloid dopamine transmission.

The mesoaccumbens dopamine pathway exhibits an enhanced dopaminergic response to a challenge injection of d-amphetamine or cocaine after repeated intermittent exposure to that drug. Much research has focused on the potential role of this sensitised response in the enhanced propensity of drug-associated stimuli to elicit relapse. However, the amygdala is acknowledged to play a critical role in stimulus-reward learning, and recent work suggests that the mesoamygdaloid dopamine pathway exerts a significant influence upon amygdala function. In the present study, rats were administered d-amphetamine (1 mg/kg, I.P.) or vehicle once per day, for 14 days. After 11 untreated days, a locomotor assay showed that prior repeated administration of d-amphetamine led to a markedly enhanced locomotor response to 0.5 mg/kg d-amphetamine. There was no effect of d-amphetamine pretreatment upon the response to a novel environment, or to injection with vehicle. Following a total of 14 days in the home cage, subjects were implanted with microdialysis probes within the amygdala, and for comparison also within the nucleus accumbens. Baseline and d-amphetamine-stimulated (0.5 mg/kg) levels of extracellular dopamine were assessed for each brain region. Results showed that baseline levels of dopamine were very similar in sensitised and control animals. By contrast, prior treatment with d-amphetamine enhanced dopamine overflow in response to a challenge with d-amphetamine both in the nucleus accumbens and amygdala. These results indicate that changes in the pattern of dopamine transmission both in the nucleus accumbens, and the amygdala, accompany the behavioural sensitisation observed after repeated exposure to d-amphetamine. Hence, an enhanced propensity of drug-associated stimuli to elicit relapse may not depend solely upon changes relating to the mesoaccumbens dopamine projection.

Amphetamine↗
PubMed1997

Cross-sensitisation with d-amphetamine following repeated intra-perifornical sulpiride infusions.

Infusions of the dopamine D2/D3 receptor antagonist sulpiride within the perifornical region of the lateral hypothalamus have been reported to increase locomotor activity. The current investigation examined the effect of repeated lateral hypothalamic sulpiride infusions. In experiment la, rats were placed repeatedly in an activity chamber either prior to, or following an infusion of 10 micrograms sulpiride or vehicle. Repeated infusions of sulpiride prior to, but not following exposure to the activity chamber increased locomotor activity during subsequent sessions. In experiment 1b, repeated pretreatment with intra-perifornical sulpiride prior to placement within the activity chamber was found to engender a significant increase in conditioned activity when placed subsequently within the same chamber drug-free. Alternatively, pretreatment with sulpiride in the home cage was found subsequently to engender a significant increase in locomotor activity during a test session with intra-perifornical sulpiride. In experiment 2, repeated pretreatment with intra-perifornical sulpiride significantly increased the locomotor response to a subsequent systemic challenge with d-amphetamine. Animals pretreated in the home cage exhibited a moderate increase in activity over vehicle controls, while animals repeatedly pretreated immediately prior to placement in the activity chamber exhibited the largest response subsequently to d-amphetamine of any group. Experiment 3 showed that repeated sulpiride infusions either 1 mm anterior or 1 mm posterior to the perifornical region were without effect upon locomotor activity. These data are suggested to reflect an indirect action of intra-perifornical sulpiride upon the mesoaccumbens dopamine projection, via the level of the ventral tegmental area. Precise neural mechanisms are under current investigation.

Amphetamine↗
PubMed1997

Isolation rearing enhances the locomotor stimulant properties of intra-perifornical sulpiride, but impairs the acquisition of a conditioned place preference.

Previous data indicated that infusions of the D2/D3 dopamine receptor antagonist sulpiride within the perifornical region of the lateral hypothalamus may engage neural circuitry relevant to activation of the mesoaccumbens dopamine projection. The present work examined this proposition further. Experiment 1 examined the ability of intra-perifornical sulpiride to induce a conditioned place preference, using an unbiased conditioning procedure. Thus, bilateral guide cannulae were implanted to gain access to the perifornical region of the lateral hypothalamus. Following recovery, animals were subjected to an initial exposure to the place preference apparatus. The apparatus consisted of three distinctive compartments, the central compartment allowing access to the two outermost compartments. Initial exposure indicated equal preference for each. Then, in alternating sessions, animals received infusions of sulpiride (5, 10 or 20 micrograms) before being placed in one of the two outermost compartments, and infusions of vehicle before being placed in the alternate compartment. Compartment-drug pairings were counterbalanced across animals. Four drug, and four saline sessions were completed, each being separated by at least 2 full days. On the final test day, animals were allowed free access to compartments, and the time spent in each was compared with that of initial exposure. Results showed that intra-perifornical sulpiride increased activity during drug-conditioning sessions in an incremental fashion, and supported dose-dependently the acquisition of a conditioned place preference. Experiment 2 examined the effects of isolation rearing upon the locomotor stimulant properties of intra-perifornical sulpiride, and the acquisition of a conditioned place preference. Rats were raised from weaning either alone (isolation-reared) or in groups of five (socially-reared controls) until 4 months of age. Consistent with previous reports of the effects of isolation rearing upon psychomotor stimulant responsivity, here isolates were found to be more responsive to the locomotor stimulant properties of intra-perifornical sulpiride, but were less responsive to the ability of intra-perifornical sulpiride to support the acquisition of a conditioned place preference. These data were suggested to provide further support for the proposition that blockade of dopamine receptors of the D2 family within the perifornical region of the lateral hypothalamus results in the activation of the mesoaccumbens dopamine projection, via the ventral tegmental area.

Animals↗
PubMed1997

Enhanced stimulus-reward learning by intra-amygdala administration of a D3 dopamine receptor agonist.

The amygdala is considered to be a critical neural substrate underlying the formation of stimulus-reward associations, and is known to receive substantial innervation from dopaminergic neurons located within the ventral mesencephalon. However, relatively little is known about the function of the mesoamygdaloid dopamine projection in stimulus-reward learning. Recently, we have found post-session intra-amygdala microinjections of d-amphetamine to enhance appetitive Pavlovian conditioning as assessed in a discriminative approach task. In the present study, we have examined the effects of dopamine receptor agonists possessing relative selectivity for the D1, D2 and D3 receptor subtypes in order to examine more fully the role of the mesoamygdaloid dopamine projection in stimulus-reward learning. Thus, subjects were trained to associated an initially neutral stimulus (CS+) with 10% sucrose reward (US). A second, control stimulus (CS-) was also presented but never paired with sucrose reward. In order to measure specifically the conditioned response to CS+/CS- presentation, responding during CS and US presentations was measured separately. Immediately following each training session, subjects received bilateral intra-amygdala infusion of 0.1, 1 or 10 nmol/side of SKF-38393, quinpirole or 7-OH-DPAT. Infusions of SKF-38393 or quinpirole were without effect on CS+ approach. However, post-session intra-amygdala infusions of 7-OH-DPAT enhanced selectively CS+ approach in a dose-dependent fashion. No dose of any drug affected CS- approach, US behaviours, or measures of extraneous behaviour. Subsequent acquisition of a novel conditioned instrumental response was also unaffected. Thus, the present data indicate a selective involvement of the D3 dopamine receptor subtype in the modulation of stimulus-reward learning by the mesoamygdaloid dopamine projection.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension in systemic sclerosis.

Pulmonary hypertension (PHT) is an important complication of systemic sclerosis (SSc). Echocardiography can be used to detect PHT and, with Doppler echocardiography, the pulmonary arterial systolic pressure (PASP) can often be estimated. We have undertaken a study to compare echocardiographic assessment with right heart catheterization (RHC) in 33 SSc patients in whom clinical assessment [including ECG, chest X-ray, lung function tests and high-resolution computed tomography (HRCT) had raised strong suspicion of PHT. The mean (S.D.) interval between echocardiography and RHC was 1.8 (2.3) months. Twenty-one patients (64%) had PHT (PASP > or = 30 mmHg) on RHC, and echocardiography correctly identified 19 of these (sensitivity 90%). Of the 12 patients without PHT on RHC, nine were correctly identified by echocardiography (specificity 75%). The five incorrectly classified patients all had PASP in the borderline normal/abnormal range. The presence of tricuspid regurgitation allowed Doppler measurement of PASP in 20 patients (61%) and this correlated significantly with RHC values (r = 0.83, P < 0.001). We conclude that echocardiography is a reliable method for detecting PHT and it may be particularly useful for the early detection and monitoring of this potentially fatal complication in SSc.

Adult↗
PubMed1997

An early anaesthetic in Papua New Guinea.

A search for information about early anaesthetics administered in Papua New Guinea has revealed that an ether or chloroform anaesthetic was given, probably for a retained placenta, at Port Hunter on December 9, 1880. The anaesthetist or anaesthetic assistant was the Reverend George Brown, a Wesleyan Methodist missionary.

Anesthesia↗
PubMed1996

Day ophthalmic surgery: aspects of perioperative care.

At Flinders Medical Centre in Adelaide, eye surgery under local anaesthesia (peribulbar block) has been carried out in the day ophthalmic surgery unit since 1987. In a subset of 536 patients, 112 patients required additional anaesthesia (supplementary retrobulbar block or regional muscle infiltration) to achieve full ocular paresis, and 10 patients required intraoperative supplementation of anaesthesia because of discomfort. Six patients had their surgery postponed (one had a retrobulbar haemorrhage and five became anxious after the procedure commenced). Sedation was rarely required and there were no adverse effects of the anaesthetic on surgical procedures or patients' vision. The authors conclude that peribulbar block provides satisfactory anaesthesia and that day ophthalmic surgery is safe and effective.

Adult↗
PubMed1996

Tumor necrosis factor alpha (rhTNF) fails to stimulate angiogenesis in the rabbit cornea.

BACKGROUND: The objective of this study was to thoroughly examine the in vivo angiogenesis activity of human recombinant tumor necrosis factor alpha (rhTNF). METHODS: rhTNF (0.5 ng to 1.0 microgram) was incorporated into the slow release polymers Hydron or HYPAN and implanted into the rabbit cornea. Release of biologically active rhTNF from the polymers was determined with the L929 cytotoxicity assay. RESULTS: All concentrations tested failed to elicit capillary formation beyond that observed for controls. Less than 2% of the rhTNF was released from the Hydron over 7 days. HYPAN released five times the amount of rhTNF in vitro, but even at doses of 500 ng (104.3 ng suggested release) no angiogenesis was stimulated. CONCLUSIONS: Under the circumstances tested, rhTNF is not angiogenic in vivo.

Acrylic Resins↗
PubMed1996

The biological, social and clinical bases of drug addiction: commentary and debate.

This article summarizes the main discussions at a meeting on the biological, social and clinical bases of drug addiction focused on contemporary topics in drug dependence. Four main domains are surveyed, reflecting the structure of the meeting: psychological and pharmacological factors; neurobiological substrates; risk factors (including a consideration of vulnerability from an environmental and genetic perspective); and clinical treatment. Among the topics discussed were tolerance, sensitization, withdrawal, craving and relapse; mechanisms of reinforcing actions of drugs at the behavioural, cognitive and neural levels; the role of subjective factors in drug dependence; approaches to the behavioural and molecular genetics of drug dependence; the use of functional neuroimaging; pharmaceutical and psychosocial strategies for treatment; epidemiological and sociological aspects of drug dependence. The survey takes into account the considerable disagreements and controversies arising from the discussions, but also reaches a degree of consensus in certain areas.

Brain↗
PubMed1995

Preoperative assessment and postoperative management of the elderly surgical patient.

The population undergoing surgery is aging and this trend will continue for many decades to come. Better anaesthetic and surgical techniques are lowering the risk-benefit ratio for surgery, making it an increasingly attractive treatment option. Good preoperative assessment and postoperative management form an integral part of strategies to minimise morbidity and mortality while maximising hospital efficiency.

Aged↗
PubMed1995

Age-related alterations in the morphology of femoral artery vasa vasorum in the rat.

The objective of this study was to explore any age-related morphological changes in the vasa vasorum of the rat femoral artery. Vascular corrosion casts were prepared from 2, 12 and 24-month-old rats. Examination of the casts with the scanning electron microscope revealed dramatic differences in the appearance of the vessels of young and aged rats. The vasa vasorum of 2-month-old rats consisted of a dense network of capillaries. These vessels were dramatically reduced in number by 12 months, and even fewer capillaries were present at 24 months. This reduction in capillary density is consistent with the observed age-related decreases in oxygen tension and may explain why the aged are more prone to atherosclerosis.

Aging↗
PubMed1995

Analysis of the effects of intra-accumbens SKF-38393 and LY-171555 upon the behavioural satiety sequence.

The outcome of intra-accumbens infusions of the dopamine D1 receptor family agonist SKF-38393 and the D2 receptor family agonist LY-171555 upon measures taken during the behavioural satiety sequence was assessed (0.01 micrograms, 0.1 micrograms, 1.0 micrograms in each case). Each drug was infused either separately, or together as a co-infusion in order to examine the functional relationship between these dopamine receptor subtypes within the nucleus accumbens. Measures of feeding did not change following infusions of SKF-38393 or LY-171555, whether infused separately or together. However, following separate infusion of the lowest dose tested of each drug (0.01 micrograms), the onset of resting was advanced. Moderate to high doses of SKF-38393 and LY-171555 (0.1 micrograms, 1.0 micrograms) infused separately resulted in a marked increase in activity at the expense of resting. Co-infusion of 0.01 micrograms of each drug also resulted in a dramatic increase in activity. Thus, measures of feeding behaviour were unchanged following excitation of D1 and D2 dopamine receptor families within the nucleus accumbens. In marked contrast, locomotor behaviour appeared to be under the potent synergistic control of these receptor families.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Proliferation of wound derived capillary endothelial cells: young versus aged.

The objective of this study was to compare the proliferative potential of wound derived capillary endothelial cells (WCEC) from aged and young rats. Endothelial cells were isolated from subcutaneously implanted sponges in 2- and 24-month-old rats. The identity of the cells as endothelial was confirmed by staining for Ac-LDL uptake. Aged and young WCEC (20,000/well) were stimulated with increasing concentrations of fetal calf serum (0, 2.5, 5, 10 and 15%). The increase in cell number was determined with a Coulter counter. At all serum concentrations, the proliferative capacity of WCEC from aged rats was significantly higher than that of WCEC from young rats.

Aging↗
PubMed1994

Mesoaccumbens dopamine-opiate interactions in the control over behaviour by a conditioned reinforcer.

These experiments examined the role of dopamine-opiate interactions in the ventral tegmental area (VTA) and nucleus accumbens in the mediation of reinforcement-related behaviour. It has been shown previously that opiates induce a dopamine-dependent increase in locomotor activity in rats when infused into the VTA, and a dopamine-independent hyperactivity when infused into the nucleus accumbens. The present study investigated the generality and significance of these two findings, by examining dopamine-opiate interactions in the control over behaviour exerted by a conditioned reinforcer (CR), an arbitrary stimulus which gains control by association with primary reinforcement. Rats were trained to associate a light/noise stimulus with sucrose reinforcement, and the efficacy of the CR in controlling behaviour was assessed by measuring its ability to support a new lever pressing response. Responding on one lever (CR lever) produced the CR, responding on the other lever had no programmed consequences. In experiment 1, intra-accumbens infusions of d-amphetamine (10 micrograms), the D1 dopamine receptor agonist SKF-38393 (0.1 microgram), the D2 dopamine receptor agonist LY-171555 (quinpirole; 0.1 microgram) or the opiate receptor agonist [D-Ala2]-methionine enkephalinamide (DALA; 1 microgram) selectively increased responding on the CR lever. Infusion with DALA intra-VTA had no effect. However, pretreatment with DALA intra-VTA (10 x 1 microgram/day) subsequently reduced the selectivity of the response to infusions intra-accumbens with d-amphetamine or SKF-38393, and blocked the response to LY-171555 or DALA. Pretreatment also shifted to the right the dose-response function for DALA intra-accumbens. In experiment 2, intra-accumbens infusions of d-amphetamine, SKF-38393, LY-171555 or DALA again increased responding on the CR lever only. Pretreatment with intra-accumbens d-amphetamine (5 x 1 microgram/day) reduced the selectivity of the response subsequently to d-amphetamine, and blocked the response to SKF-38393, LY-171555 or DALA. In experiment 3, intra-accumbens infusions of the mu-opiate receptor agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (0.003-0.1 microgram), or the delta-opiate receptor agonist [D-Pen2,5]-enkephalin (0.03-1 microgram) enhanced selectively responding on the CR lever. Thus, the dopamine-dependent locomotor-stimulant properties of intra-VTA infusions of opiates are associated with impaired conditioned reinforcer efficacy. Finally, repeated stimulation of the mesoaccumbens dopamine pathway may compromise the dopamine-independence of the opiate system within the nucleus accumbens.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Isolation rearing enhances the locomotor response to cocaine and a novel environment, but impairs the intravenous self-administration of cocaine.

Male Lister hooded rats were raised from weaning either alone (isolation reared) or in groups of five (socially reared controls). At 5 months of age, experiments began. Experiment 1 examined the effect of isolation rearing upon the locomotor response to a novel environment, and the locomotor stimulant effect of an injection of cocaine (10 mg/kg). Isolation reared animals were more active in a novel environment, and were more responsive to the locomotor stimulant action of cocaine. In succeeding experiments, the effects of isolation rearing on the reinforcing efficacy of intravenous cocaine were assessed. Animals were never "primed" with noncontingent infusions of cocaine at any time during these experiments. In experiment 2, the effect of isolation rearing upon the acquisition of the intravenous self-administration of cocaine was examined. Two levers were present in the operant chambers. Depression of one lever resulted in the intravenous delivery of a 1.5 mg/kg infusion of cocaine, responses on the second, control lever were recorded but had no programmed consequences. Isolation reared animals acquired a selective response on the drug lever at a slower rate than socially reared controls. In experiment 3, a full cocaine dose-response function was examined. Isolation rearing shifted the cocaine dose-response function to the right. In addition, isolation rearing impaired the selectivity of the response on the drug lever at lower doses of cocaine. In experiment 4, the effect of isolation rearing upon the response to a conditioned reinforcer associated previously with cocaine delivery was observed. In the absence of cocaine, the contingent presentation of the conditioned reinforcer enhanced selectively the rate of response by socially reared controls. However, isolation reared animals were unresponsive to this manipulation. These data are discussed with reference to dysfunctional cortico-limbic-striatal systems, and their interactions with the mesoaccumbens dopamine projection.

Animals↗