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D B Neill

Publications and source records attributed to D B Neill.

At least 19 recordsLinked to original sources

Optimality under noise: higher memory strategies for the alternating prisoner's dilemma.

The Alternating Prisoner's Dilemma is a variant of the iterated Prisoner's Dilemma in which the players alternate in the roles of actor and recipient. We searched for strategies which are "optimal" in the Alternating Prisoner's Dilemma with noise (a non-zero probability that a player's decision will be transmitted incorrectly). In order to achieve success against a variety of other strategies, a strategy must be "self-cooperating" (able to achieve mutual cooperation with its clone), "C-exploiting" (able to exploit unconditional cooperators), and "D-unexploitable" (able to resist exploitation by defectors). It must also have high evolutionary "dominance", a general measure of evolutionary performance which considers both resistance to invasion and the ability to invade other strategies. A strategy which meets these optimality criteria can evolve cooperation by invading a population of defectors and establishing a stable cooperative society. Most of the strategies commonly discussed in the Alternating Prisoner's Dilemma literature are low-memory strategies such as Tit For Tat, Pavlov, and Firm But Fair, but none of these strategies can simultaneously meet all of the optimality criteria. However, we discovered a class of higher memory "Firm Pavlov" strategies, which not only meet our stringent optimality criteria, but also achieve remarkable success in round-robin tournaments and evolutionary interactions. These higher memory strategies are friendly enough to cooperate with their clone, pragmatic enough to exploit unconditional cooperators, and wary enough to resist exploitation by defectors: they are truly "optimal under noise" in the Alternating Prisoner's Dilemma.

Algorithms↗

Dopamine D1/D2 agonists injected into nucleus accumbens and ventral pallidum differentially affect locomotor activity depending on site.

Ventral pallidal dopamine has been recently shown to play an important role in psychostimulant reward and locomotor activation. The aim of the present study was to compare the roles of ventral pallidal D1 and D2 receptors in evoking locomotor activity with those in the nucleus accumbens. The D1 agonist SKF 38393 and the D2 agonist quinpirole hydrochloride (0.3-3 microg/ 0.5 microl) were bilaterally injected into ventral pallidum or nucleus accumbens through pre-implanted cannulae. In the ventral pallidum, 0.3-1 microg SKF 38393 increased locomotor activity while 3 microg had no effect; 3 microg quinpirole suppressed locomotion while 0.3-1 microg had no effect. Locomotor activity induced by an equigram (0.3 microg) mixture of SKF 38393 and quinpirole, while significantly higher than that induced by 0.3 microg quinpirole was not significantly higher than that induced by 0.3 microg SKF 38393 alone. At the 3 microg dose, SKF 38393 injections into anterior ventral pallidum increased activity; injections into posterior ventral pallidum decreased activity. In the nucleus accumbens, 0.3-3 microg SKF 38393 dramatically increased locomotor activity while quinpirole moderately increased locomotion. In the group that had previously received the full quinpirole dose range, injection of the equigram (0.3 microg) mixture of SKF 38393 and quinpirole induced locomotor activation which was higher than that induced by either drug alone or by the addition of the effect of each drug alone, i.e. synergy occurred. Moreover, rats that had previously received SKF 38393 developed a sensitized locomotor response to subsequent SKF 38393, quinpirole or the mixture of these two drugs. The difference in locomotor response to dopamine agonists between the ventral pallidum and nucleus accumbens is consistent with electrophysiological evidence collected at these two sites. These findings suggest that, unlike the nucleus accumbens, where D1 and D2 receptor activation may facilitate each other to induce a synergistic effect on locomotor activity, ventral pallidal D1 and D2 receptors may be located on different neurons and coupled with different, if not opposite, behavioral output.

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

GABAergic modulation of ventral pallidal dopamine release studied by in vivo microdialysis in the freely moving rat.

The mesopallidal dopamine system, which originates from the ventral tegmental area and projects to the ventral pallidum (VP), has been recently shown to play an important role in self-stimulation reward and cocaine reward. VP also receives a GABAergic projection from nucleus accumbens (NAS). The aim of the present study was to examine the involvement of this GABAergic projection in the modulation of VP dopamine release. Both the GABAA antagonist picrotoxin (2-200 microM) and the GABAB antagonist phaclofen (20-2,000 microM), perfused locally, dose-responsively increased VP extracellular dopamine 2-2.5-fold. Cocaine (10 microM) produced a 6.5-fold increase of VP dopamine. Neither picrotoxin (200 microM), phaclofen (2,000 microM), nor GABA (20-2,000 microM) altered the response of VP dopamine to locally applied cocaine. GBR 12909 (0.5 microM), a selective dopamine uptake blocker, induced a 3.5-fold increase of VP dopamine. The increase of VP dopamine in response to GBR 12909 was further augmented to 8.5-fold of baseline when picrotoxin (200 microM) was added to the perfusate. The data from the present study demonstrate that the GABAergic NAS-VP projection can modulate ventral pallidal dopamine release. However, the effect of GABA on the mesopallidal dopamine system's response to locally applied cocaine may be complicated by actions of cocaine other than dopamine uptake inhibition.

Animals↗

Locomotor response to novelty does not predict cocaine place preference conditioning in rats.

Previous studies have demonstrated that rats showing a strong locomotor response to a novel environment have a greater locomotor response to psychostimulant drugs and more rapidly acquire intravenous self-administration of amphetamine. In this report, we examined whether these high-responder (HR) rats would develop place-preference conditioning with cocaine more readily than low-responder (LR) rats. Neither group of rats developed conditioned place preference for cocaine, 2.5 mg/kg, intraperitoneally (IP). Both groups of rats developed conditioned place preference for cocaine, 5.0 and 15 mg/kg, IP. However, we could not find any evidence of enhanced conditioning in the HR rats. HR rats did show a greater locomotor response to cocaine, 15 mg/kg, IP, and the locomotor response of HR and LR rats to cocaine correlated with their response to a novel environment. We conclude that using the place-preference procedure, HR and LR rats do not differ in the rewarding effect of cocaine.

Animals↗

Locomotor response to novelty does not predict cocaine place preference conditioning in rats.

Previous studies have demonstrated that rats showing a strong locomotor response to a novel environment have a greater locomotor response to psycho-stimulant drugs and more rapidly acquire intravenous self-administration of amphetamine. In this report, we examined whether these high-responder (HR) rats would develop place-preference conditioning with cocaine more readily than low-responder (LR) rats. Neither group of rats developed conditioned place preference for cocaine, 2.5 mg/kg, intraperitoneally (IP). Both groups of rats developed conditioned place preference for cocaine, 5.0 and 15 mg/kg, IP. However, we could not find any evidence of enhanced conditioning in the HR rats. HR rats did show a greater locomotor response to cocaine, 15 mg/kg, IP, and the locomotor response of HR and LR rats to cocaine correlated with their response to a novel environment. We conclude that using the place-preference procedure, HR and LR rats do not differ in the rewarding effect of cocaine.

Animals↗

Increased sensitivity to cocaine place-preference conditioning by septal lesions in rats.

Rats bearing electrolytic lesions of medial septum and sham-operated controls were trained on cocaine place-preference in a 3-compartment apparatus. Cocaine was paired with a white or a black compartment. An unbiased design was used, in which cocaine was paired with the preferred side in half the animals and with the unpreferred side in the other half. Two low doses of cocaine HCl were used: 2.5 and 5.0 mg/kg. Only two pairings of drug with environment were used to minimize the influence of drug sensitization. Rats with septal lesions, but not controls, showed preference conditioning to the black side at 2.5 mg/kg; lesioned and control animals showed similar conditioning to the black side at 5.0 mg/kg. Lesioned animals could not be conditioned to the white side at either dose. This was attributed to a drug-induced enhancement of a previously described increased reactivity to brightness following septal lesions. Controls conditioned to either side at 5.0 mg/kg. It was concluded that septal lesions lowered the cocaine dose required for preference conditioning, consistent with reports that such damage enhances some behavioral effects of psychostimulants.

Animals↗

Individual differences in schedule-induced and conditioned behaviors.

Previous experiments have shown that subjects which exhibit a high locomotor response to novelty (HR) also show a greater locomotor response to psychomotor stimulants than subjects which have a low locomotor response to a novel environment (LR). The current experiments were designed to examine in more detail the behavioral differences between HR and LR rats in non-drug paradigms. In the first experiment HR rats acquired schedule-induced polydipsia (SIP) more readily than LR rats. Panel pressing to gain access to the food pellets, however, was greater in LR rats compared to HR rats, especially after stable levels of SIP had been attained. In the second experiment one group of rats were fed daily after a 30-min period in photocell-cages (food conditioning; FC) while a control group was fed in the home-cage (non-conditioned; NC). FC subjects developed heightened locomotor activity in anticipation of feeding in the initial 30 min in the test-cage compared to NC rats. This anticipatory locomotor activity developed more rapidly and to a greater level in HR rats than in LR rats. The concentrations of dopamine, dihydroxyphenylacetic acid, homovanillic acid, serotonin, 5-hydroxyindoleacetic acid, and norepinephrine were determined at the completion of behavioral testing in both the food conditioned and non-conditioned rats. The food conditioned experiment showed that variations in both the dopaminergic and serotoninergic systems may underlie individual differences in behavioral responsiveness. However, no clear pattern of neurochemical differences emerged. The current set of experiments have demonstrated differences between HR and LR rats in non-drug related paradigms and that HR rats appear to show a greater motivational excitement induced by periodic food delivery than LR rats.

Animals↗

Assessment of the relative contribution of peripheral and central components in cocaine place conditioning.

A balanced place conditioning paradigm was used to assess the contribution of peripheral and central factors mediating place conditioning induced by cocaine HCl. The first experiment was conducted to examine changes in locomotor activity and extracellular dopamine (DA) concentrations in the nucleus accumbens (NACC) following intraperitoneal (IP) injections of cocaine HCl (15 mg/kg) or cocaine methiodide (19.6 mg/kg). IP cocaine HCl significantly increased locomotor activity and extracellular NACC DA, whereas IP cocaine methiodide failed to increase either locomotor activity or extracellular DA in the NACC. In the second experiment, IP cocaine HCl (15 mg/kg) induced a significant conditioned place preference; however, neither IP procaine HCl (25 or 50 mg/kg) nor IP cocaine methiodide (4.9, 9.8, or 19.6 mg/kg) induced preferences for the drug-paired compartment. In the third experiment, intracerebroventricular (ICV) infusions of cocaine HCl (25 micrograms/2 microliters) or cocaine methiodide (1 or 5 micrograms/2 microliters) induced significant place conditioning for the drug-paired compartment. These results suggest place conditioning induced by cocaine HCl is mediated centrally and that the local anaesthetic properties alone do not contribute to this effect to any significant degree.

Animals↗

Decreased raphe unit activity in a rat model of endogenous depression.

One theory about the pathogenesis of endogenous depression is that decreased serotonergic (5-HT) neurotransmission is involved in producing the disorder. A key component of brain 5-HT neurotransmission is the discharge rate of 5-HT neurons in the dorsal raphe nucleus (DRN), a major aggregation of 5-HT neurons. We tested the hypothesis that the discharge rate of 5-HT neurons in the DRN was decreased in a new animal (rat) model of human endogenous depression. In this model, rats are treated neonatally with the antidepressant chlorimipramine. When adult, these animals exhibit several behavioral, REM sleep, and treatment response features of the human disorder. We found in a single unit measurements in adult, pentobarbital-anesthetized rats that, compared with 'non-depressed' control rats, the 'depressed' rats had a lower discharge rate of 5-HT neurons in the DRN. This correlation is consistent with the theory that 5-HT neurotransmission is diminished in endogenous depression.

Animals↗

6-Hydroxydopamine lesions of the medial prefrontal cortex fail to influence cocaine-induced place conditioning.

This study investigated the involvement of medial prefrontal cortex (mPFC) dopamine in cocaine place conditioning using a totally balanced place conditioning design. Presynaptic dopamine terminals of the mPFC were lesioned by bilaterally infusing the selective neurotoxin 6-hydroxydopamine (6-OHDA). These lesions significantly depleted dopamine (-83%) and norepinephrine (-70%) in the mPFC but there were no significant reductions in either the nucleus accumbens or in the caudate-putamen compared with sham-operated controls. Furthermore, serotonin levels were not affected in any of the brain regions investigated. These lesions failed to attenuate place conditioning induced by the intraperitoneal (i.p. 10 mg/kg) administration of cocaine when compared to sham lesioned controls. In addition, there were no significant differences in spontaneous locomotor activity between the two groups during the preconditioning phase or the test phase. These results suggest that 6-OHDA lesions which produced profound depletions of dopamine and norepinephrine in the mPFC did not alter the rewarding efficacy of cocaine as measured by the place conditioning paradigm.

Animals↗

Conditioned locomotor activity but not conditioned place preference following intra-accumbens infusions of cocaine.

In the first experiment, the conditioned place preference (CPP) paradigm was used to examine the rewarding properties of bilateral microinfusions of cocaine HCl into the nucleus accumbens (0, 12.5, 25, 50, or 100 micrograms). No dose of intra-accumbens cocaine induced a significant CPP. However, bilateral intra-accumbens infusions of d-amphetamine sulfate (10 micrograms) or intraperitoneal administration of cocaine HCl (5 or 10 mg/kg) both produced a significant preference for the drug-paired compartment. In the second experiment, the ability of bilateral intra-accumbens infusions of cocaine HCl (50 micrograms) to elicit conditioned locomotor activity (CLA) was examined. During the conditioning trials, intra-accumbens cocaine significantly increased locomotor activity. On the test day, when no drug was administered, the group that had previously received cocaine in the activity chamber showed significantly greater locomotor activity than the vehicle control group. This demonstration of CLA indicates that rats are able to associate the effects of intra-accumbens infusions of cocaine with environmental stimuli; however, these infusions are not rewarding as measured by the CPP paradigm. In addition, these results may indicate important differences between the neural substrates for cocaine and amphetamine reward and reveal a dissociation between CPP and CLA.

Amphetamine↗

Individual differences in amphetamine sensitization: dose-dependent effects.

Rats were screened for locomotor activity in a novel environment and divided into high (HR) or low (LR) responders based on whether their locomotor score for the first hour was above or below the median. In the first experiment, HR and LR rats were compared for their locomotor response following repeated administration of either 0.0, 0.5, 1.0, or 1.5 mg/kg d-amphetamine sulfate (AMPH). Injections of either 0.5 or 1.0 mg/kg AMPH produced higher locomotor activity in HR rats than in LR rats. Furthermore, there was a correlation between the locomotor response to novelty and the response to either 0.5 or 1.0 mg/kg AMPH. In addition, whereas both groups of rats developed the same degree of sensitization to 0.5 mg/kg AMPH, only the HR rats developed pronounced sensitization to repeated administration of 1.0 mg/kg AMPH. When both HR and LR were considered, there was a significant correlation between response to novelty and the extent of sensitization to the locomotor-stimulating properties of 1.0 mg/kg AMPH. There were no differences in locomotor activity or sensitization between HR and LR rats following the highest dose of AMPH (1.5 mg/kg). In a separate experiment, HR and LR rats were compared for locomotor activity following a series of intracranial infusions of AMPH. There were no overall differences in locomotor activity between the HR and LR groups following AMPH infusions into either the nucleus accumbens (NACC) or the anterior dorsal striatum (ADS). However, the locomotor activity scores in the novel environment significantly correlated with the locomotor response to 3.0 micrograms AMPH infused into either the NACC or ADS.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

Response to novelty predicts the locomotor and nucleus accumbens dopamine response to cocaine.

The relationship between a rat's locomotor response to a novel environment and its behavioral and dopaminergic responses to cocaine was examined. Subjects were divided into two groups based on their locomotor response to a novel environment. Subjects who had a novelty response above the median were classified as high responders (HR), while those with a novelty response below the median were classified as low responders (LR). Following administration of cocaine-HCl (0, 2.5, 5.0, 10.0, or 15.0 mg/kg), HR rats showed a greater locomotor response than LR rats. Moreover, there was a significant correlation between a subject's locomotor response to the novel environment and the locomotor response to either 10.0 (r = 0.65) or 15.0 (r = 0.92) mg/kg cocaine. In a separate experiment, the extracellular concentration of dopamine in the nucleus accumbens (NACC) was monitored using microdialysis procedures. Following cocaine administration (15.0 mg/kg) HR rats showed a larger NACC dopamine response and greater locomotor activity than LR rats. In addition, there was a threefold greater locomotor activity to dopamine ratio in HR rats than in LR rats. A correlation between a subject's locomotor response to a novel environment and the dopaminergic response to cocaine was also evident. These results suggest that differences in the locomotor response to cocaine can, to some degree, be predicted by a rat's locomotor response to a novel environment, and that variations in dopamine-dependent mechanisms of the NACC may underlie these individual differences.

Animals↗

Individual differences in locomotor activity and sensitization.

Male rats were screened for locomotor activity in a novel environment and divided into high (HR) and low (LR) responders based on whether their locomotor activity score for the first hour was above or below the median locomotor activity for the subject sample. Subsequently, the locomotor response to repeated administration of either amphetamine (AMPH; 0.5 mg/kg), cocaine (10 mg/kg), scopolamine (0.5 mg/kg) or saline was monitored in separate groups of HR and LR rats. HR rats had significantly higher overall activity scores than LR rats for all 3 drugs. Both HR and LR rats developed tolerance at the same rate to repeated scopolamine administration. In contrast, only HR rats showed pronounced sensitization to the locomotor stimulating properties of AMPH and a direct correlation was evident between the locomotor response to novelty and the magnitude of sensitization. These results suggest that an individual's response to a novel environment can, to a certain extent, predict drug-induced locomotor activity and that individual differences in the response to novelty and sensitization to AMPH may result from individual variations in a common neural mechanism.

Amphetamine↗

Dopamine release at behaviorally relevant parameters of nigrostriatal stimulation: effects of current and frequency.

Released dopamine was monitored voltammetrically in the rat striatum in response to electrical stimulation of the nigrostriatal bundle. Stimulation parameters encompassed those typically used in behavioral studies. Dopamine released during intracranial self-stimulation (ICSS)-like stimulation reached a maximum within the first minute of stimulation, then rapidly decreased. The pattern of release obtained with continuous stimulation as a function of current and frequency supports the view that as the stimulation current is increased, a greater number of neurons are stimulated, while increasing the frequency of stimulation results in a fixed population of neurons being stimulated more intensely. Computer modeling of stimulated release from a population of dopaminergic nerve terminals was used to interpret effects of current and frequency and to predict ICSS release patterns as a function of schedule of reinforcement.

Animals↗

Caffeine elevates reinforcement threshold for electrical brain stimulation: tolerance and withdrawal changes.

Caffeine dose-dependently increased the reinforcement threshold for electrical self-stimulation of the brain in rats, which is opposite to the effect of other behavioral stimulants. Tolerance to this effect of caffeine developed rapidly with daily drug administration. Abrupt cessation of daily drug treatment was followed by decreases in reinforcement threshold and response rate lasting 24-48 h, changes consistent with a drug withdrawal phenomenon. Because caffeine has the characteristics of a drug of abuse, these results question the generality of hypotheses relating the abuse potential of a drug to its ability to sensitize brain reward systems.

Animals↗

Detecting behaviorally relevant changes in extracellular dopamine with microdialysis.

A method is described for monitoring extracellular levels of striatal dopamine in the rat during behavior. The extracellular fluid is sampled using a microdialysis probe modified for use in behaving animals. Dopamine concentration in the perfusate is determined every 5 min using an automated smallbore chromatographic system with electrochemical detection. The system is capable of detecting behaviorally related changes of 5 nM, in extracellular dopamine.

Animals↗