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Biomedical subjects

A Dickinson

Publications and source records attributed to A Dickinson.

At least 37 records · Page 2Linked to original sources

The role of withdrawal in heroin addiction: enhances reward or promotes avoidance?

The compulsive nature of heroin abuse has been attributed to the fact that drug self-administration enables an addict to escape from and avoid the severe withdrawal symptoms resulting from opiate dependence. However, studies of incentive learning under natural motivational states suggest an alternative hypothesis, that withdrawal from heroin functions as a motivational state that enhances the incentive value of the drug, thereby enabling it to function as a much more effective reward for self-administration. In support of this hypothesis, we show here that previous experience with heroin in withdrawal is necessary for subsequent heroin-seeking behavior to be enhanced when dependent rats once again experience withdrawal.

Animals↗

Involvement of the central nucleus of the amygdala and nucleus accumbens core in mediating Pavlovian influences on instrumental behaviour.

Pavlovian conditioned cues exert a powerful influence on instrumental actions directed towards a common reward, this is known as Pavlovian-to-instrumental transfer (PIT). The nucleus accumbens (NAcc) has been hypothesized to function as an interface between limbic cortical structures required for associative conditioning, like the amygdala, and response mechanisms through which instrumental behaviour can be selected and performed. Here we have used selective excitotoxic lesions to investigate the involvement of subnuclei of the amygdala as well as the core and shell regions of the nucleus accumbens on PIT in rats. Within the amygdala, selective lesions of the central nucleus (CeN), but not of the basolateral nucleus (BLA), abolished the PIT effect. In addition, selective lesions of the NAcc core, but not the NAcc shell, also abolished PIT. None of the lesions impaired the acquisition of Pavlovian food cup approaches or instrumental responding itself. These data demonstrate that the CeN and NAcc core are central components of the neural system mediating the impact of Pavlovian cues on instrumental responding. We suggest that this effect may depend upon the regulation of the dopaminergic innervation of the NAcc core by projections from the CeN to the ventral tegmental area.

Amygdala↗

Peyronie's disease-the Plymouth experience of extracorporeal shockwave treatment.

OBJECTIVE: To describe our experience of the use of extracorporeal shockwave treatment (EST) for Peyronie's disease. Patients and methods The study included 28 patients (mean age 57 years, range 34-72) with stable Peyronie's disease who were treated with 3.9 (3-5) sessions of EST to the Peyronie's plaque. The patients' erectile function, pain and penile angle were assessed before and after treatment with EST. RESULTS: Of the 28 patients, 20 felt that their erection improved after the procedure; 11 patients were able to recommence sexual intercourse and the index of erectile function increased in all but one patient. Conclusion EST produces a significant improvement in pain and penile angle, with no serious complications.

Adult↗

The 28th Bartlett Memorial Lecture. Causal learning: an associative analysis.

The concordance between performance and judgements of the causal effectiveness of an instrumental action suggests that such actions are mediated by causal knowledge. Although causal learning exhibits many associative phenomena--blocking, inhibitory or preventative learning, and super-learning--judgements of the causal status of a cue can be changed retrospectively as a result of learning episodes that do not directly involve the cue. In order to explain retrospective revaluation, a modified associative theory is described in which the learning processes for retrieved cue representations are the opposite to those for presented cues, and this theory is evaluated by studies of the role of within-compound associations in retrospective revaluation and blocking. However, this modified theory only applies when the within-compound association represents a contiguous rather than a causal cue relationship.

Animals↗

Re-examination of the role of within-compound associations in the retrospective revaluation of causal judgements.

We investigated blocking and retrospective revaluation of causal judgements using a scenario in which food cues acted as potential causes of an allergic reaction as the outcome. In the blocking contingency, the treatment cues were either paired or unpaired with the outcome prior to a second stage in which sequential compounds of treatment and target cues were paired with the outcome. The order of this compound and treatment training was reversed in retrospective revaluation contingencies. When the interstimulus interval between the treatment and target cues was unfilled on compound trials (Experiments 1 and 3), both blocking and retrospective revaluation were observed in that the target cue trained in compound with the paired treatment cue attracted lower causal ratings than the target cue trained in compound with the unpaired treatment cue. By contrast, performing a mental arithmetic task using numerals presented during the interstimulus interval had no effect on the magnitude of blocking but rendered retrospective revaluation unreliable (Experiments 2 and 3). These results provide further support for accounts of revaluation based upon within-compound associations.

Adult↗

Scrub jays (Aphelocoma coerulescens) form integrated memories of the multiple features of caching episodes.

Four experiments examined whether food-storing scrub jays remember when and where they cached different foods. The scrub jays cached and recovered perishable and nonperishable foods in visuospatially distinct and trial-unique cache sites. They rapidly learned to avoid searching for foods that had perished by the time of recovery, while continuing to search for the same foods after shorter retention intervals when the foods were still fresh. The temporal control of searching at recovery was also observed when the familiarity of cache sites did not provide any information about the time of caching and when the same food was cached in distinct sites at different times. The authors argue that the jays formed an integrated memory for the location and time of caching of particular foods.

Animals↗

Cocaine seeking by rats is a goal-directed action.

In two experiments rats were trained to self-administer intravenous cocaine on chained schedules using different responses in the initial (drug-seeking) and terminal (drug-taking) links. In both between- (Experiment 1) and within-subject designs (Experiment 2), the drug-taking response was then either extinguished or reinforced in the absence of the opportunity to perform the seeking response. In a subsequent extinction test with the seeking manipulanda alone, the rate of drug seeking was reduced after the prior extinction of the associated taking response. An additional group trained with a sucrose reinforcer showed a comparable devaluation effect. These findings demonstrate that seeking responses for cocaine and food rewards are mediated by a representation of the contingency between seeking responses and the opportunity to take the reward.

Animals↗

The effect of lesions of the insular cortex on instrumental conditioning: evidence for a role in incentive memory.

In three experiments, we assessed the effect of lesions aimed at the gustatory region of the insular cortex on instrumental conditioning in rats. In experiment 1, the lesion had no effect on the acquisition of either lever pressing or chain pulling in food-deprived rats whether these actions earned food pellets or a maltodextrin solution. The lesion did, however, attenuate the impact of outcome devaluation, induced by sensory-specific satiety, on instrumental performance but only when assessed in an extinction test. This effect was not secondary to an impairment in instrumental learning; in experiment 2, no evidence was found to suggest that the lesioned rats differed from shams in their ability to encode the specific action-outcome contingencies to which they were exposed during training. In experiment 3, however, lesioned rats were found to be insensitive to the impact of an incentive learning treatment conducted when they were undeprived; although, again, this deficit was confined to a test conducted in extinction. These results are consistent with the view that, in instrumental conditioning, the gustatory region of the insular cortex is involved in encoding the taste of food outcomes in memory and, hence, in encoding the incentive value assigned to these outcomes on the basis of prevailing motivational conditions.

Analysis of Variance↗

Examination of the human prion protein-like gene doppel for genetic susceptibility to sporadic and variant Creutzfeldt-Jakob disease.

A novel human gene named Doppel (DPL) that has homology to the prion protein gene (PRNP) has recently been identified on chromosome 20p. By automated sequencing we have found a common (M174T, 48%) and an uncommon coding polymorphism. The polymorphic frequency of the M174T allele was examined in cases of variant and sporadic Creutzfeldt-Jakob Disease and compared with the frequency in the normal UK population. In sharp distinction to the M129V polymorphism of PRNP we have not found any evidence of disease association nor is there any association with age of onset, disease duration, or prion protein (PrP(Sc)) strain type.

Chromosomes, Human, Pair 20↗

Family fighting.

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Adolescent↗

Video playground.

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Adolescent↗

Cocaine-seeking by rats: regulation, reinforcement and activation.

RATIONALE: In animal models of drug self-administration, response rates often decrease with dose suggesting that a regulative process may mask the reinforcing effects of the drug. OBJECTIVE: The purpose of the present experiments was to dissociate the role of regulative and reinforcement processes in intravenous cocaine self-administration by rats using a paradigm that explicitly distinguishes between drug-seeking and drug-taking. METHODS: Rats were trained to respond for intravenous cocaine (0.25 mg/infusion) under a heterogeneous chain (tandem FR1 RI 30 s) FR1 schedule of reinforcement using different levers in the first (seeking) and second (taking) links of the chain. After 10 days of training, rats were switched to one of three doses of cocaine (0.08, 0.25, or 0.5 mg/infusion) and self-administration patterns were recorded for a further ten sessions in experiment 1. In experiment 2, a time-out (TO) period (0, 4, or 12 min) was imposed between successive cycles of the chain schedule. Finally, the effect of allowing animals to perform a drug-taking response on subsequent drug-seeking was assessed in experiment 3. RESULTS: Having verified that seeking responses for a conventional reinforcer (sucrose) were sensitive to changes in reward magnitude, experiment 1 demonstrated that the number of self-administered infusions was inversely related to dose whereas the latency to initiate drug-seeking increased with dose. Variations in the cocaine dose had no reliable effect on the number of drug seeking response per cycle of the chain schedule. The effect of dose on the latency to initiate drug-seeking was reversed in experiment 2 with increasing TO periods. Moreover, at the longest TO period, drug-seeking responses per cycle increased and the latency to initiate drug seeking decreased with dose. Experiment 3 showed that the latency to drug-seek for the low dose was reduced dramatically when the first drug-seeking response was preceded by a drug-taking response, even when this response did not produce a drug infusion. CONCLUSIONS: The overall pattern of results suggests that drug-seeking and drug-taking are controlled by three interacting processes: a regulative process depresses drug-seeking in the short-term; behavioral activation enhances drug-seeking and is sustained over longer intervals by higher drug doses; the reinforcing effect of cocaine increases with dose once the satiety producing effects of the drug dissipate.

Animals↗

Can cord blood cells support the cytokine storm in GvHD?

Cord blood has a high number of proliferating hematopoietic progenitors and is therefore used as an alternative source of hematopoietic cells for allogeneic transplantation. In addition there is a wider availability of cord blood and a lower cost of procurement compared to bone marrow. However one of the most interesting immunological benefits of a cord blood transplant that has been proposed is the low severity of Graft versus Host Disease (GvHD). This review aims to address some of the immunological reasons why this may be the case by assessing the role of cord blood cytokines in the cytokine storm of GvHD.

Animals↗