Biomedical subjects

Jane R Taylor

Publications and source records attributed to Jane R Taylor.

27 records · Page 2Linked to original sources

PubMed2003

Nicotine enhances responding with conditioned reinforcement.

RATIONALE: The mesolimbic dopamine system has been implicated in the primary reinforcing properties of drugs of abuse as well as in enhanced responding with conditioned reinforcement produced by psychomotor stimulant drugs. Despite clinical observations that nicotine self-administration (i.e. smoking) depends strongly upon conditioned reinforcement (i.e. cues support smoking behavior), little is known about whether nicotine directly affects motivational processes. OBJECTIVE: In these experiments, we investigated whether acute nicotine would influence responding with conditioned reinforcement and the degree to which pretreatment with the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine would modify any nicotine-induced behavioral effects. METHODS: After subjects had been trained to associate an initially neutral stimulus with water reward, they received acute nicotine (43,25-350 micro g/kg SC; -5 min) or saline injections and were tested on the acquisition of a new response for conditioned reinforcement paradigm. In separate experiments, the effect of pretreatment with the nicotinic acetylcholine receptor antagonist mecamylamine (300 or 1000 micro g/kg SC; -20 min) alone, or in combination with nicotine (350 micro g/kg SC; -5 min), on conditioned reinforcement was also examined. RESULTS: Acute nicotine injection produced a selective enhancement of responding with conditioned reinforcement (i.e. on the CR lever), without producing non-selective increases in overall responding. The effect of nicotine (350 micro g/kg SC; -5 min) was selectively blocked by mecamylamine (300 micro g/kg). CONCLUSIONS: These findings demonstrate that acute exposure to nicotine augments the control over behavior by a conditioned reinforcer, suggesting that nicotine may enhance motivational processes.

Animals↗

PubMed2003

Repeated nicotine exposure enhances reward-related learning in the rat.

Repeated exposure to addictive drugs causes neuroadaptive changes in cortico-limbic-striatal circuits that may underlie alterations in incentive-motivational processes and reward-related learning. Such drug-induced alterations may be relevant to drug addiction because enhanced incentive motivation and increased control over behavior by drug-associated stimuli may contribute to aspects of compulsive drug-seeking and drug-taking behaviors. This study investigated the consequences of repeated nicotine treatment on the acquisition and performance of Pavlovian discriminative approach behavior, a measure of reward-related learning, in male rats. Water-restricted rats were trained to associate a compound conditioned stimulus (tone+light) with the availability of water (the unconditioned stimulus) in 15 consecutive daily sessions. In separate experiments, rats were repeatedly treated with nicotine (0.35 mg/kg, s.c.) either (1) prior to the onset of training, (2) after each daily training session was completed (ie postsession injections), or (3) received nicotine both before the onset of training as well as after each daily training session. In this study, all nicotine treatment schedules increased Pavlovian discriminative approach behavior and, thus, prior repeated exposure to nicotine, repeated postsession nicotine injections, or both, facilitated reward-related learning.

Animals↗

PubMed2003

Sex-related differences in spatial divided attention and motor impulsivity in rats.

The acquisition and performance of a self-paced test of spatial divided attention linked with frontal cortex function were assessed in postpubertal (> 60 days) normal or gonadectomized male and female rats. Males were more accurate at detecting relatively brief visual stimuli than females, but this difference was eliminated by increasing the target stimulus duration, indicating an attentional basis for this effect. Premature errors were, however, greater in males than in females, suggesting greater impulsivity in males. Subsequent experiments in gonadectomized rats suggest that circulating hormones influence attention and impulsivity, but not necessarily sex differences. These results demonstrate a double dissociation between components of impulse control and divided attention in male and female rats and may have implications for sex differences in disorders of attention and cognition.

Animals↗

PubMed2003

Molecular and behavioral interactions between central melanocortins and cocaine.

Behavioral and molecular studies have established a link between drugs of abuse and the central melanocortin system, particularly the melanocortin 4 receptor (MC4-R). The present study expands this line of investigation to characterization of the neurochemical and behavioral interactions between MC4-R and the psychomotor stimulant, cocaine. The results demonstrate that repeated, but not acute, cocaine administration up-regulates MC4-R mRNA expression in the striatum and hippocampus, but not cerebral cortex. Pharmacological studies indicate that the up-regulation of MC4-R expression occurs via dopamine D1 and D2 receptor-dependent mechanisms. The D1/D2 antagonist haloperidol and the D2-selective antagonist eticlopride mimic the effect of cocaine on MC4-R expression. In addition, coadministration of a D1-selective antagonist, SCH 23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine], completely blocks the up-regulation of MC4 mRNA by cocaine, demonstrating that D1 receptor activation is necessary for this response. Moreover, the results demonstrate that cocaine treatment increases behavioral responses (grooming and locomotor activity) to infusions of a melanocortin agonist, indicating that up-regulation of MC4-R expression results in functional consequences. These data further support a role for the melanocortin-MC4-R neuropeptide system in the biochemical and behavioral effects of cocaine.

Analgesics, Opioid↗

PubMed2003

Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability.

OBJECTIVE: Epidemiological studies indicate that experimentation with addictive drugs and onset of addictive disorders is primarily concentrated in adolescence and young adulthood. The authors describe basic and clinical data supporting adolescent neurodevelopment as a biologically critical period of greater vulnerability for experimentation with substances and acquisition of substance use disorders. METHOD: The authors reviewed recent literature regarding neurocircuitry underlying motivation, impulsivity, and addiction, with a focus on studies investigating adolescent neurodevelopment. RESULTS: Adolescent neurodevelopment occurs in brain regions associated with motivation, impulsivity, and addiction. Adolescent impulsivity and/or novelty seeking as a transitional trait behavior can be explained in part by maturational changes in frontal cortical and subcortical monoaminergic systems. These developmental processes may advantageously promote learning drives for adaptation to adult roles but may also confer greater vulnerability to the addictive actions of drugs. CONCLUSIONS: An exploration of developmental changes in neurocircuitry involved in impulse control has significant implications for understanding adolescent behavior, addiction vulnerability, and the prevention of addiction in adolescence and adulthood.

Adaptation, Psychological↗

PubMed2002

Stimulation of protein kinase a activity in the rat amygdala enhances reward-related learning.

BACKGROUND: Drug addiction in humans is associated with abnormal metabolic activity within the amygdala and heightened control of behavior by drugs and drug-related (conditioned) stimuli. Drug-induced neuroadaptations, including activation of cAMP (cyclic adenosine monophosphate)-dependent protein kinase A (PKA), within the amygdala may contribute to the synaptic plasticity and reward-related learning that underlies pathologic behavior in addicted individuals. METHODS: In this study, we tested the hypothesis that stimulation of PKA activity within the rat amygdala would facilitate the acquisition of Pavlovian approach behavior, a measure of reward-related learning. RESULTS: Intraamygdala infusions of Sp-cAMPS (which activates PKA) produced concentration-dependent enhancements of the acquisition of approach to a conditioned stimulus that predicted water availability; intraamygdala infusions of cholera toxin (which elevates cAMP levels) produced a similar effect. Conversely, intraamygdala infusions of Rp-cAMPS, an inhibitor of PKA, impaired acquisition of approach behavior. CONCLUSIONS: Together, these data demonstrate that stimulation of PKA activity in the amygdala can facilitate reward-related learning and suggest that neuroadaptative changes in the PKA pathway within this brain region may be a mechanism by which chronic drug abuse alters the control of behavior by drug-associated stimuli.

Adjuvants, Immunologic↗

PubMed2002

Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP-treated monkeys: feasibility relevant to multiple-target grafting as a therapy for Parkinson's disease.

Transplantation of embryonic dopamine (DA) neurons is being studied as an experimental replacement therapy for the DA-deficiency characteristic of Parkinson's disease. Some studies suggest that one of the limitations of this approach is that intrastriatal placement of implants fails to consistently restore completely normal movement. One potential cause of this suboptimal therapeutic outcome is that changes in the neural activity of several structures in the basal ganglia circuitry resulting from striatal DA depletion is not adequately normalized by graft-derived DA replacement in striatum alone. In the present study, we assessed the feasibility of grafting embryonic DA neurons into the substantia nigra (SN) of adult parkinsonian monkeys as an approach to restoration of the DA modulation of striatal-nigral afferents that is lost after degeneration of SN neurons. Sixteen St. Kitts African green monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) received implants of embryonic monkey ventral mesencephalon (VM), or sham implants, aimed at the rostral SN. At 6 months after grafting, staining for tyrosine hydroxylase (TH) indicated that grafted DA neurons survived at this site, albeit often in reduced numbers compared with VM grafts to striatum. Grafted neurons extended neurites into the parenchyma of the SN, but there was no evidence of lengthy extension of graft-derived neurites rostrally along the trajectory of the mesostriatal fiber system. A region-specific, modest increase in DA levels and TH-positive fiber density in the ventral-medial putamen was detected, accompanied by modest but significant decreases in parkinsonian behaviors at 5-6 months after grafting. Our findings support the view that grafting embryonic tissue to the SN is a feasible procedure in nonhuman primates that provides a modest but detectable benefit of its own. These results encourage the further development of multiple-target grafting strategies as a means of restoring modulation of anatomically widespread basal ganglia structures relevant to treatment of Parkinson's disease.

Animals↗

PubMed2002

Impairments of reversal learning and response perseveration after repeated, intermittent cocaine administrations to monkeys.

The current experiments examined the effects of acute or repeated, intermittent administrations of cocaine on the acquisition and reversal of object discriminations by Vervet monkeys in order to test the hypothesis that cocaine treatment affects performance of tasks that depend upon the functions of the orbitofrontal cortex and amygdala. An acute dose of cocaine (1 mg/kg; 20 min prior to testing) impaired reversal of a previously learned object discrimination but had no effect on acquisition of a novel one. Specific impairments of reversal learning were also observed in monkeys 9 and 30 days after repeated administrations of cocaine (2 or 4 mg/kg, once daily for 14 days) that were perseverative in nature, indicating persistent behavioral consequences of repetitive dosing. The results indicate that repeated cocaine administrations produce enduring impairments of object discrimination learning when the inhibition of a previously conditioned response is required. These findings suggest that long-term cocaine administration may disrupt orbitofrontal efferents to the striatum, resulting in impaired inhibition of established conditioned responses.

Animals↗

PubMed2002

An animal model of Tourette's syndrome.

OBJECTIVE: An animal model was used to investigate an autoimmune etiology for some cases of Tourette's syndrome. METHOD: Sera from 12 patients with Tourette's syndrome with high levels of antineural or antinuclear antibodies were infused bilaterally into the ventrolateral striatum of rats. Sera from 12 additional Tourette's syndrome patients and 12 normal subjects (both groups with low levels of autoantibodies) were infused for comparison. Rates of oral stereotypies were recorded by observers who were blind to the origin of the infused sera. RESULTS: Oral stereotypies significantly increased in the rats infused with sera from the patients with high levels of autoantibodies. CONCLUSIONS: The results are consistent with an autoimmune etiology in a subset of cases of Tourette's syndrome.

Adolescent↗