Biomedical subjects

Anthony G Phillips

Publications and source records attributed to Anthony G Phillips.

28 records · Page 2Linked to original sources

PubMed2003

Interleukin 1 beta enhances conditioned fear memory in rats: possible involvement of glucocorticoids.

Central administration of 15 ng interleukin (IL)-1beta in the rat significantly enhanced conditioned fear memory assessed by a passive avoidance task, when retested at 24 and 48 h post-training. Pain threshold was unaffected by 15 ng IL-1beta administration. IL-1beta treatment also increased serum corticosterone. This increase in serum corticosterone was further enhanced in rats given both IL-1beta and footshock. Furthermore, the glucocorticoid receptor antagonist mifepristone blocked IL-1beta-induced elevation in corticosterone and also attenuated the enhanced conditioned fear memory. Central administration of IL-1beta significantly increased prostaglandin E2 and decreased the anti-inflammatory cytokine IL-10 release from whole blood cultures; therefore this treatment appears to be effective in inducing an inflammatory response in both the periphery and the brain. The present study confirms that IL-1beta can enhance conditioned fear memory, an effect which is correlated with changes in glucocorticoid function. This facilitation of defensive behaviour could reflect adaptive responses which may enhance survival during sickness.

Animals↗

PubMed2003

A waitlist control-group study of cognitive, mood, and quality of life outcome after posteroventral pallidotomy in Parkinson disease.

OBJECT: The aim of this study was to examine neuropsychological outcome from unilateral posteroventral pallidotomy (PVP) in Parkinson disease while controlling for confounding factors such as test practice and disease progression. METHODS: Participants underwent baseline and 2-month follow-up assessments of cognition, quality of life, mood, and motor functioning. The surgery group (22 patients) underwent PVP (15 left, seven right) after baseline assessment. The waitlist group (14 patients) underwent PVP after follow up. At follow up, the left PVP group exhibited a decline on verbal measures of learning, fluency, working memory, and speeded color naming. The incidence of significant decline on these measures after left PVP ranged from 50 to 86%. The right PVP group did not exhibit a significant cognitive decline, but fluency did decline in 71% of patients who underwent right PVP. Participants who underwent PVP reported better bodily pain and social functioning at follow up than participants in the waitlist group. Improved bodily pain was evident for 62% of the surgery group, and social functioning improved for 19%. Surgery did not alter reported physical functioning or mood. Dyskinesia improved after surgery, but there were no improvements in "on-state" manual dexterity or handwriting. CONCLUSIONS: Most patients who underwent left PVP exhibited declines in learning, fluency, working memory, and speeded color naming. Accounting for retesting effects altered the magnitude of these declines by up to one quarter of a standard deviation, but did not increase the breadth of postsurgical neuropsychological decline beyond that typically reported in the literature. It was found that PVP improved dyskinesia, bodily pain, and social functioning, but did not lead to improvement on other objective and self-reported measures of motor functioning.

Aged↗

PubMed2002

Modulation by central and basolateral amygdalar nuclei of dopaminergic correlates of feeding to satiety in the rat nucleus accumbens and medial prefrontal cortex.

Current studies raise the possibility that subregions within the amygdala may interact with the mesocorticolimbic dopamine (DA) system to subserve specific psychological processes underlying food reward. The present study compared the effect of reversible inactivation of the central nucleus (CeN) versus the basolateral amygdala (BLA) on DA efflux in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) in hungry rats that were tested in a food-devaluation procedure. During DA microdialysis experiments, lidocaine, a sodium channel blocker, was delivered via reverse dialysis into the CeN or BLA while rats were given two consecutive meals of Froot Loops. Loss of CeN function impaired the development of satiety during an initial meal and, consequently, diminished the effect of devaluation by satiety on intake of the same food during a second meal. Inactivation of the CeN was also associated with decreased basal levels of DA efflux in the NAc before food intake and attenuated increases in DA efflux related to anticipatory and consummatory aspects of feeding in both the NAc and mPFC. In contrast, inactivation of the BLA did not affect feeding behavior or DA efflux. Overall, these findings indicate that the CeN and BLA independently modulate DA transmission in both terminal regions. It is proposed that interaction between the CeN and mesocorticolimbic DA activity may be a mechanism by which hunger and satiety signals influence the value of food reward, or alternatively, a mechanism by which memory for a recently consumed food regulates food intake.

Amygdala↗

PubMed2002

Dopamine release in human ventral striatum and expectation of reward.

Using the ability of [11C]raclopride to compete with dopamine for D(2)/D(3) receptors, we investigated by positron emission tomography the effect of placebo (saline) injection on dopamine release in the ventral striatum of patients with Parkinson's disease. We found evidence for placebo-induced dopamine release of similar magnitude to that reported in healthy volunteers after amphetamine administration. However, in contrast to the dorsal striatum, there were no differences in [11C]raclopride binding potential changes between patients who experienced the reward (those who reported placebo-induced clinical benefit) and those who did not. We conclude that the release of dopamine in the ventral striatum (nucleus accumbens) is related to the expectation of reward and not to the reward itself. These observations have potential implications for the treatment of drug addiction.

Antiparkinson Agents↗

PubMed2002

Glutamate receptor-dependent modulation of dopamine efflux in the nucleus accumbens by basolateral, but not central, nucleus of the amygdala in rats.

Dopaminergic neurotransmission in the nucleus accumbens (NAc) and neural processes in the basolateral (BLA) and central (CeN) amygdala nuclei are implicated in associative reward learning. Given their direct and indirect connections with the NAc and ventral tegmental area (VTA), both the BLA and CeN may regulate the mesoaccumbens dopamine (DA) system in rewarding situations. Electrical stimulation of the BLA (20 Hz, 10 sec, 300 microA) induced a long-lasting 25 +/- 4% increase in DA efflux in the NAc, measured by microdialysis in freely moving rats, whereas comparable stimulation of the CeN had no effect. Reverse dialysis of either the NMDA receptor antagonist APV (100 micrometer) or the AMPA-kainate receptor antagonist DNQX (100 micrometer), but not the metabotropic glutamate receptor antagonist (+/-)-amino-4-carboxy-methyl-phenylacetic acid (100 micrometer), into the NAc blocked the stimulation-evoked increase in DA efflux in the NAc. VTA infusion of lidocaine (lido; 4%) significantly reduced basal DA levels for approximately 30 min but failed to suppress the increase in NAc DA efflux resulting from BLA stimulation. Additionally, infusions of lido (4%) into the medial prefrontal cortex failed to block the stimulation-evoked increase in NAc DA efflux. These data support the hypothesis that the BLA can directly modulate DA efflux through local mechanisms in the NAc, independent of an action on DA cell bodies in the VTA. The finding that brief activation of the CeN had no long-lasting effects on DA efflux in the NAc suggests an important degree of functional independence between the CeN and BLA.

Amygdala↗

PubMed2002

Inhibition of dopamine efflux in the rat nucleus accumbens during abstinence after free access to d-amphetamine.

Abstinence following 'binge' use of psychostimulants is hypothesized to be related to a depletion of synaptic dopamine (DA) in the nucleus accumbens. The present study, therefore, tested the pharmacological responsiveness of the mesolimbic DA system to d-amphetamine injections, measured by in vivo chronoamperometry with stearate-modified graphite paste electrodes, during voluntary abstinence when rats were given prolonged free availability to d-amphetamine. Rats self-administered i.v. d-amphetamine (FR-1 time out 30 s; 0.25 mg/kg per inf) in three sessions, each separated by approximately 24 h, (1) to a criterion of 12 infusions; (2) for 24 h and (3) for 48 h. During the third session, when self-administration had ceased for at least 1.5 h (abstinence), and DA levels were near, or below, pre-drug baseline values, rats received passive i.v. injections of d-amphetamine or vehicle in a pattern that mimicked self-administration patterns during the first hour of the 48 h session. In contrast to the significant increases in DA efflux observed during the first hour of self-administration, d-amphetamine injections during abstinence did not increase DA oxidation currents. Furthermore, the length of the abstinence period was correlated with the time required for DA to return to pre-abstinence values. Together, these results suggest that the mesolimbic DA system is pharmacologically unresponsive to the actions of d-amphetamine during abstinence, and that resumption of drug use is associated with 'recovery of function' in the mesolimbic DA system.

Animals↗

PubMed2002

A 'crash' course on psychostimulant withdrawal as a model of depression.

Most drugs of abuse generate diverse behavioral and neurochemical effects in mammals. However, one feature common to many such drugs is the phenomenon of the withdrawal syndrome that results from termination of drug administration. Early drug withdrawal, often referred to as the 'crash' phase in humans, is characterized by adverse psychological and/or somatic symptoms. Withdrawal from psychostimulant drugs precipitates a transient and primarily psychological condition that bears remarkable similarity to the symptoms of major depressive disorder in humans. Rodent paradigms of psychostimulant withdrawal faithfully model the human condition. Associated behavioral deficits in these animals can be reversed by treatments with antidepressant properties, suggesting that psychostimulant withdrawal might provide the basis for an animal model of depression. Current advances and limitations in the development of this model, together with recent evidence that psychostimulant withdrawal in rodents can be used to screen for novel, rapidly acting antidepressant treatments, are discussed.

Animals↗

PubMed2002

Exposure to repeated, intermittent d-amphetamine induces sensitization of HPA axis to a subsequent stressor.

Previous studies have demonstrated that exposure to psychostimulant drugs can produce a lasting cross-sensitization to the behavioral effects of stress. The main purpose the present study was, therefore, to determine the effects of psychostimulant cross-sensitization on the stress-induced release of adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Rats were given a series of injections of d-amphetamine or vehicle in a regimen that has been shown previously to induce cross-sensitization to a stressor. After two weeks, half the animals in the drug and vehicle-treated conditions were subjected to 30 min restraint stress; the remaining animals served as non-stressed controls. Animals were then sacrificed and trunk blood was assayed for CORT and ACTH. Prior d-amphetamine had no effect upon levels of CORT and ACTH in the non-stressed animals. Following 30 min restraint stress, however, levels of both hormones were significantly higher in drug-treated animals compared to controls. A second experiment confirmed behavioral sensitization to the current schedule of d-amphetamine injections, and demonstrated neuroendocrine sensitization of ACTH and CORT to a subsequent drug challenge. The augmented release of CORT and ACTH observed in d-amphetamine-treated rats might have important implications for human disorders in which processes resembling neurochemical sensitization have been hypothesized to play an etiological role.

Adrenocorticotropic Hormone↗

PubMed2001

Repeated electroconvulsive shock attenuates the depressive-like effects of d-amphetamine withdrawal on brain reward function in rats.

RATIONALE: The withdrawal of humans from high doses of psychostimulant drugs can result in a transient syndrome which appears isomorphic to endogenous depression. One of the more prominent symptoms is a loss of hedonic capacity; in animals, the anhedonia associated with amphetamine withdrawal has been measured objectively by decrements in responding for intracranial self-stimulation (ICSS). OBJECTIVE: To date, the effects of amphetamine withdrawal on ICSS responding have been reversed by different antidepressant drugs. In the present study, we sought to reverse withdrawal-induced anhedonia by administration of repeated electroconvulsive shocks (ECS). METHODS: Rats with electrodes in the lateral hypothalamus were trained on an ascending-series current intensity ICSS paradigm until stable levels of responding were attained. Half of the animals were then administered a 4-day escalating dose schedule of d-amphetamine, and tests for ICSS responding started 12 h after the final injection. During withdrawal, all animals received daily treatment with either ECS or sham-ECS. RESULTS: Amphetamine withdrawal was associated with reduced ICSS responding; animals treated with ECS exhibited a facilitated recovery compared to sham-ECS treated animals, and returned to control levels of ICSS responding 24 h earlier. CONCLUSIONS: ECS was able to mitigate the anhedonic effects of d-amphetamine withdrawal, and provides additional support for the use of psychostimulant withdrawal as a model of depression.

Animals↗

PubMedDate not supplied

Increased successive negative contrast in rats withdrawn from an escalating-dose schedule of D-amphetamine.

The exposure of humans and animals to high doses of psychostimulant drugs, followed by their withdrawal, leads to a number of aversive psychological symptoms. These symptoms include increased anxiety and anhedonia, and may be manifested behaviorally as a decreased interest in normally rewarding stimuli. In the present study, we determine the effects of withdrawal from an escalating-dose schedule of D-amphetamine on the consumption of a 4% sucrose solution under normal conditions, and after an incentive downshift. The downshift was induced by subjecting animals to a consumatory negative contrast paradigm, by switching them from a familiar 32% sucrose solution to a novel 4% solution. In unshifted animals, there was no effect of D-amphetamine withdrawal on consumption of the 4% solution. In contrast, drug-withdrawn animals displayed an exaggerated negative contrast effect, primarily reflected as a delayed recovery from the downshift lasting for at least 60 h. This effect is interpreted as a consequence of the increased emotionality of withdrawn animals, and may be related to disruption of normal search behaviors.

Animals↗