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At least 1,279 records · Page 71Linked to original sources
PubMed2003

Nicotine as a signal for the presence or absence of sucrose reward: a Pavlovian drug appetitive conditioning preparation in rats.

RATIONALE: In Pavlovian conditioning research, nicotine is typically conceptualized as the unconditioned stimulus (US) that becomes associated with an exteroceptive conditioned stimulus (CS). This research has not explored the possibility that nicotine can also function as a CS. OBJECTIVES: The present research examined whether nicotine served as a CS for the presence (CS+) or absence (CS-) of sucrose and started defining its specificity. METHODS AND RESULTS: Rats trained in the CS+ condition had nicotine (0.4 mg/kg, base) paired intermittently with brief access to sucrose. Intermixed were saline sessions without sucrose. Nicotine acquired the ability to evoke goal tracking. This conditioned response (CR) decreased across extinction sessions. The CR was sensitive to nicotine dose (ED(50)=0.113 mg/kg) and administration to testing interval; 0-min and 100-min delays produced no CR. The CS properties were specific to nicotine in that amphetamine and bupropion substitution was incomplete. Rats in the CS- condition received similar discrimination training except that sucrose was paired with saline. Nicotine also served as a CS-; the saline state CS+ acquired control of goal tracking. Mecamylamine, but not hexamethonium, blocked nicotine's ability to serve as a CS+ and CS-, indicating a role for central nicotinic acetylcholine receptors. CONCLUSIONS: Nicotine served as a signal for the presence or absence of sucrose. The extinction, CS-, and substitution results eliminated a psychomotor stimulant account. The conceptualization of nicotine as a CS suggests novel empirical research in which a drug acquires additional inhibitory and/or excitatory value based on other outcomes present during its effects.

Animals↗
PubMed2004

Second-order stimuli do not always increase overall response rates in second-order schedules of reinforcement in the rat.

RATIONALE: Second-order schedules of reinforcement have been used extensively to model reward-seeking and drug-seeking behaviour. Second-order stimuli within second-order schedules have been shown to enhance response rates during operant responding for natural reinforcers and drug reinforcers. This has led some to view second-order schedules of drug reinforcement as a model maintained of drug-seeking in addicts by drug-associated stimuli. However, the functional role of the second-order stimulus within second-order schedules is complex. OBJECTIVE: We investigated the role of second-order stimuli within a second-order schedule of reinforcement [FI 4 min (FR10: S)] maintained by sweetened water reinforcement. METHODS: Eight rats were trained to press a bar on a second-order schedule of reinforcement and tested in the presence and absence of the second-order stimulus. RESULTS: In contrast to most previous work, overall bar-pressing rates were significantly increased when the second-order stimulus was omitted (second-order stimulus omission: 0.17 Hz (+/-0.04, 95% CI); second-order stimulus present: 0.13 Hz (+/-0.04, 95% CI)). However, second-order stimuli also changed the pattern of responding whereby rats would make a bout of bar presses prior to the presentation of the second-order stimulus and then pause briefly after the second-order stimulus. In the absence of second-order stimuli, responding was uniformly high. Control measures, such as the ability of the second-order stimulus to evoke checking for the primary reinforcers, indicated that the second-order stimulus was associated with the primary reinforcer. CONCLUSIONS: These results demonstrated that although second-order stimuli maintained responding and caused the rat to check for primary reinforcement, overall response rates were increased when the second-order stimuli were omitted. This has implications for interpreting the results of studies where overall response rates within second-order schedules have been the only measure used to assess the effects of potential anti-addiction drugs. Future studies could be improved by performing a second-order stimulus omission test analysing both the overall response rates and the temporal organization of responding with respect to the second-order stimulus.

Analysis of Variance↗
PubMed2005

Centrally administered orexin A increases motivation for sweet pellets in rats.

RATIONALE: Centrally administered orexin A induces both feeding and locomotion in rats. Thus, the feeding response following orexin A administration may be secondary to general increases in activity rather than a specific motivation to eat. OBJECTIVE: The aim of the study is to determine whether orexin A increases the motivation to eat. METHODS: The effect of orexin A (0, 31.25, 62.5, 125, 250, and 500 pmol) on breakpoint was determined in male Sprague-Dawley rats with rostro-lateral hypothalamic cannulae under a progressive ratio of five schedule (PR5). The effect of orexin A (0, 31.25, 125, and 500 pmol) on pressing rate under a fixed ratio (20) schedule was obtained to analyze the time course of orexin-A-induced pressing. The effect of 24-h food deprivation on breakpoint under PR5 and the effect of orexin A (125 pmol) on free feeding (sweet pellets) and on open-field locomotor activity (0, 100, 500, and 1,000 pmol) were also tested. RESULTS: Orexin A significantly augmented free feeding of sweet pellets, open-field locomotor activity, rate of pressing (FR20 schedule), and breakpoint (PR5 schedule), although compared to 24-h deprivation, the effect of orexin A on breakpoint was mild. However, there was a differential dose response relationship and time course of stimulation between orexin A's effects on locomotion and lever pressing. CONCLUSION: These data indicate that infusion of orexin A enhances free feeding by enhancing and possibly prolonging motivation to eat.

Animals↗
PubMed2005

Antidepressant-like effects of agomelatine, melatonin and the NK1 receptor antagonist GR205171 in impulsive-related behaviour in rats.

RATIONALE: Substance P receptor [neurokinin1 (NK1-R)] antagonists and melatonin(1/2) receptor (MT(1/2)-R) agonists have been claimed to be potential antidepressants (ADs). In animals, these compounds are active in validated models responsive to ADs, such as forced swimming test and chronic mild stress paradigms. Classical AD drugs are also known to be effective in pathologies characterized by an impulse control deficiency. In line with this clinical observation, previous studies demonstrated that classical ADs increased the capacity to wait for food reward in rats subjected to a paradigm aimed at assessing impulsive-related behaviour. OBJECTIVES: This study was conducted to investigate the effects of two MT(1/2)-R agonists, melatonin and agomelatine, and a NK1-R antagonist, GR205171, on tolerance to delay of food reward in rats. METHODS: Fasting rats were trained in a T-maze and allowed to choose between two magnitudes of reward: immediate but small reward (two pellets) vs 25-s delayed but large reward (ten pellets). Under this alternative, vehicle-injected rats selected the large-but-delayed reinforcer in less than 40% of the trials. RESULTS: Like the established ADs clomipramine (8 mg kg(-1), i.p.) and fluvoxamine (4 mg kg(-1), i.p.), melatonin (3 and 10 mg kg(-1), i.p.), agomelatine (10 and 30 mg kg(-1), i.p.) and GR205171 (30 mg kg(-1) but not 10 mg kg(-1), s.c.) significantly increased the number of choices of the large-but-delayed reward. The effect of melatonin (3 mg kg(-1), i.p.) was not counteracted by the MT(1/2)-R antagonist S22153 (40 mg kg(-1), i.p.) that exerted no effect on its own. CONCLUSION: These results suggest that MT(1/2)-R agonists and NK1-R antagonists enhance rats' tolerance to delay of gratification, an effect which may reflect their ability to improve impulse control. Further investigations are necessary to clarify the neurobiological mechanisms responsible for this effect.

Acetamides↗
PubMed2006

The debate over dopamine's role in reward: the case for incentive salience.

INTRODUCTION: Debate continues over the precise causal contribution made by mesolimbic dopamine systems to reward. There are three competing explanatory categories: 'liking', learning, and 'wanting'. Does dopamine mostly mediate the hedonic impact of reward ('liking')? Does it instead mediate learned predictions of future reward, prediction error teaching signals and stamp in associative links (learning)? Or does dopamine motivate the pursuit of rewards by attributing incentive salience to reward-related stimuli ('wanting')? Each hypothesis is evaluated here, and it is suggested that the incentive salience or 'wanting' hypothesis of dopamine function may be consistent with more evidence than either learning or 'liking'. In brief, recent evidence indicates that dopamine is neither necessary nor sufficient to mediate changes in hedonic 'liking' for sensory pleasures. Other recent evidence indicates that dopamine is not needed for new learning, and not sufficient to directly mediate learning by causing teaching or prediction signals. By contrast, growing evidence indicates that dopamine does contribute causally to incentive salience. Dopamine appears necessary for normal 'wanting', and dopamine activation can be sufficient to enhance cue-triggered incentive salience. Drugs of abuse that promote dopamine signals short circuit and sensitize dynamic mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Such drugs interact with incentive salience integrations of Pavlovian associative information with physiological state signals. That interaction sets the stage to cause compulsive 'wanting' in addiction, but also provides opportunities for experiments to disentangle 'wanting', 'liking', and learning hypotheses. Results from studies that exploited those opportunities are described here. CONCLUSION: In short, dopamine's contribution appears to be chiefly to cause 'wanting' for hedonic rewards, more than 'liking' or learning for those rewards.

Animals↗
PubMed2006

Ligands selective for alpha4beta2 but not alpha3beta4 or alpha7 nicotinic receptors generalise to the nicotine discriminative stimulus in the rat.

RATIONALE: Nicotine produces behavioural effects that are potentially related to its interaction with diverse nicotinic acetylcholine receptor populations. Evidence from gene deletion studies suggests that the interoceptive stimulus properties of nicotine are mediated by heteromeric high-affinity receptors containing alpha4beta2 subunits. Mice lacking beta2 subunits do not discriminate nicotine (Shoaib et al., Neuropharmacology, 42:530-539, 2002), and nicotine does not elicit dopamine release in these animals (Grady et al., J Neurochem, 76:258-268, 2001). The stimulus properties of nicotine can be detected in rats using a two-lever operant drug discrimination paradigm, allowing them to be classified pharmacologically using ligands with selectivity for receptors containing alpha4beta2, alpha3beta4 or alpha7 subunits. MATERIALS AND METHODS: Rats trained to discriminate 0.4 mg/kg nicotine from vehicle were given the nicotinic receptor agonists, cytisine, varenicline, TC2559, ABT-594, A-85380 (all having high affinity but varying selectivity for alpha4beta2-containing receptors), and WO 03/062224 and WO 01/60821A1 (selective for beta4- and alpha7-containing receptors, respectively). In separate studies, WO 03/062224 was used as the training stimulus. RESULTS: Nicotine, TC-2559, A-85380 and ABT-594 showed dose-dependent and complete stimulus substitution, whilst WO 03/062224 and WO 01/60821A1 were completely without effect. Cytisine and varenicline showed partial generalisation, consistent with their partial agonist activity at nicotinic receptors eliciting dopamine release in rat striatal slices. After almost 50 training sessions with WO 03/062224, there was no clear evidence that an alpha3beta4 receptor agonist could sustain a discriminable stimulus. CONCLUSION: Substitution to the nicotine discriminative stimulus required high-affinity and high intrinsic activity at beta2 but not at beta4- or at alpha7-containing nicotinic receptors.

Animals↗
PubMed2006

Effects of nornicotine enantiomers on intravenous S(-)-nicotine self-administration and cardiovascular function in rats.

RATIONALE: Previous neurochemical evidence indicates that R(+)-nornicotine is more potent than S(-)-nornicotine in evoking dopamine release in rat nucleus accumbens slices. OBJECTIVE: The current study tested the hypothesis that R(+)-nornicotine is also more potent than S(-)-nornicotine in selectively decreasing intravenous S(-)-nicotine self-administration in rats. RESULTS: After acute pretreatment (1-10 mg/kg for each enantiomer), R(+)-nornicotine was more potent than S(-)-nornicotine in decreasing S(-)-nicotine self-administration; in contrast, within the same dose range, the nornicotine enantiomers were equipotent in decreasing sucrose-maintained responding. This enantioselectivity does not likely reflect a difference in bioavailability, since similar levels of nornicotine were recovered from the brain 60 min after injection (5.6 mg/kg for each enantiomer). With repeated pretreatment, tolerance did not develop to the rate-decreasing effect of either nornicotine enantiomer (3 or 5.6 mg/kg) with respect to the decrease in S(-)-nicotine self-administration, although the enantioselectivity dissipated across repeated pretreatments. While both enantiomers acutely produced a similar increase in blood pressure and heart rate, tolerance developed to the blood pressure effects of R(+)-nornicotine, but not to the effects of S(-)-nornicotine, across repeated treatments. CONCLUSION: Both R(+)- and S(-)-nornicotine may have potential utility as a novel tobacco use cessation agent.

Animals↗
PubMed2007

The disruptive effects of the CB1 receptor antagonist rimonabant on extinction learning in mice are task-specific.

RATIONALE: Disruption of CB(1) receptor signaling through the use of CB(1) (-/-) mice or the CB(1) receptor antagonist rimonabant (SR141716) has been demonstrated to impair extinction of learned responses in conditioned fear and Morris water maze tasks. In contrast, CB(1) (-/-) mice exhibited normal extinction rates in an appetitively motivated operant conditioning task. OBJECTIVES: The purpose of this study was to test whether rimonabant would differentially disrupt extinction learning between fear-motivated and food-motivated tasks. MATERIALS AND METHODS: Separate groups of C57BL/6J mice were trained in two aversively motivated tasks, conditioned freezing and passive avoidance, and an appetitively motivated operant conditioning task at a fixed ratio (FR-5) schedule of food reinforcement. After acquisition, the respective reinforcers in each task were withheld, and an intraperitoneal injection of vehicle or rimonabant was given 30 min before each extinction session. RESULTS: Rimonabant (3 mg/kg) treatment significantly disrupted extinction in both the conditioned freezing and passive avoidance tasks but failed to affect extinction rates in the operant conditioning task, whether using daily or weekly extinction sessions. Interestingly, rimonabant (3 mg/kg) prevented the significant increases in lever pressing (i.e., extinction burst) that occurred during the first extinction session of the operant conditioning task. CONCLUSIONS: These results support the hypothesis that the CB(1) receptor plays a vital role in the extinction of aversive memories but is not essential for extinction of learned responses in appetitively motivated tasks.

Animals↗
PubMed1998

Effects of delivery rate and non-contingent infusion of cocaine on cocaine self-administration in rhesus monkeys.

The goal of this study was to determine whether slowly infused, response-independent cocaine would reduce cocaine self-administration in an animal model of drug abuse. Seven male rhesus monkeys self-administered i.v. cocaine on a fixed-ratio 30 schedule (5-min time-out). With unit dose (0.056 mg/kg per infusion for one monkey and 0.032 mg/kg per infusion for the rest) and infusion volume (0.5 ml) held constant, the rate of delivery was manipulated (0.125, 0.1875, 0.375, 0.75 and 3 ml/min, with infusions lasting 240, 160, 80, 40, and 10 s, respectively). Response rates increased monotonically as a function of delivery rate. Responding for cocaine at the slowest delivery rate did not differ from saline. The effects of infusing additional cocaine (starting 30 min prior to the session) at this non-reinforcing rate (0.125 ml/min) were then determined. Delivery rate of the self-administered infusion was manipulated as before. Non-contingent cocaine significantly increased responding for cocaine (at the fastest delivery rate) and for saline. While non-contingent cocaine reduced responding for cocaine in two of the seven monkeys, it also significantly reduced responding in three monkeys that responded for food on the same schedule. Plasma levels of cocaine delivered at rates of 0.125 and 3 ml/min were compared in five other monkeys. While a higher peak was reached with the faster infusion, levels did not differ after 5 min. Thus, when an infusion became available (after the 5-min time-out) in the self-administration experiments, plasma levels should not have differed regardless of the delivery rate. These results suggest that a low-dose, slow-delivery treatment with cocaine might prime or reinstate drug seeking rather than decrease it.

Animals↗
PubMed2002

Effects of cytotoxic nucleus accumbens lesions on instrumental conditioning in rats.

In two experiments the involvement of the nucleus accumbens in instrumental conditioning was investigated using rats as subjects. In experiment 1, extensive bilateral cytotoxic lesions of the nucleus accumbens mildly suppressed instrumental responding reinforced with food, but had no detectable effect on the sensitivity of the rats' performance either to outcome devaluation or to degradation of the instrumental contingency. In experiment 2, restricted accumbens lesions reliably attenuated the excitatory effect of systemically administered d-amphetamine on lever pressing for a conditioned reinforcer, and completely abolished Pavlovian-instrumental transfer. Taken together these results give a picture of the involvement of the rat nucleus accumbens in instrumental conditioning. They support the widely held theory that the nucleus accumbens mediates the excitatory effects of appetitively conditioned Pavlovian signals on instrumental performance and refute the hypothesis that the nucleus accumbens is part of the neural circuitry by which incentive value is attached to the representations of instrumental outcomes.

Animals↗
PubMed2006

Facilitated extinction of appetitive instrumental conditioning following excitotoxic lesions of the core or the medial shell subregion of the nucleus accumbens in rats.

The nucleus accumbens has been implicated in the control of goal-directed behaviour, including instrumental conditioning. Here, we evaluated the effect of N-methyl-D: -aspartate (NMDA)-induced excitotoxic lesions restricted to either the core or the medial shell subregions of the nucleus accumbens (NAC) on extinction in rats using a trial discrete fixed ratio-5 (FR-5) appetitive operant procedure. Neither core nor shell lesions of the NAC affected the acquisition of instrumental responding. Both lesions facilitated the cessation of responding when the instrumental act no longer yielded reinforcement. Our results suggest that both the NAC core and medial shell contribute to the control of extinction learning of appetitively motivated instrumental behaviour.

Analysis of Variance↗
PubMed2004

Appetence behaviours of the triatomine bug Rhodnius prolixus on a servosphere in response to the host metabolites carbon dioxide and ammonia.

A combination of 1,000 ppm CO(2) plus 30-40 ppb NH(3) in an air stream induced Rhodnius prolixus nymphs walking on a servosphere to perform a series of appetence behaviours. Shortly after the onset of stimulation the nymphs turned sharply upwind towards the source of the chemostimuli (within 13 +/- 9 s) from mostly downwind and crosswind walks in the air stream alone. The mean vector angles of these upwind tracks were concentrated in a cone 60 degrees either side of due upwind. The upwind walking bugs stopped more frequently but for a shorter duration and walked at a higher speed than before stimulation. During stops in the presence of the chemostimuli the bugs frequently corrected their course angles and extended their forelegs to reach higher with their antennae in the air. In the air stream alone, R. prolixus nymphs frequently sampled the sphere surface with the antennae and cleaned their antennae with the foreleg tarsi. However, the nymphs only briefly tapped the left or right antennal flagellum on the corresponding first leg tarsus and never touched the servosphere surface in the presence of the chemostimuli. After chemostimulus removal from the air stream the bugs continued to respond with the same appetence responses as during stimulation, but walked more tortuously in a crosswind direction in an effort to regain contact with the chemostimuli.

Administration, Inhalation↗
PubMed2005

Selective modulation of task performance by octopamine in honey bee (Apis mellifera) division of labour.

Octopamine treatment has previously been shown to increase honey bee foraging behaviour. We determined the effects of octopamine on other tasks to learn how octopamine affects division of labour in honey bee colonies. Octopamine treatment did not increase the rate of corpse removal from the hive, suggesting that elevated brain levels of octopamine do not act to increase the performance of all flight-related tasks. Octopamine treatment also did not increase attendance in the queen's retinue, suggesting that elevated brain levels of octopamine do not act to increase responsiveness to all olfactory stimuli. Consistent with these findings, octopamine treatment enhanced the foraging response to brood pheromone but not the cell capping response, a component of brood care. These results demonstrate a relatively specific form of neuromodulation by octopamine in the regulation of division of labour in honey bee colonies.

Animals↗
PubMed2006

Behavioural examination of the infrared sensitivity of rattlesnakes (Crotalus atrox).

Pitvipers (Crotalinae) and boid snakes (Boidae) possess highly sensitive infrared (IR) receptors. The ability of these snakes to image IR radiation allows the assessment of the direction and distance of an IR source (such as warm-blooded prey) in the absence of visual cues. The aim of this study was to determine the behavioural threshold of snakes to an IR stimulus. A moving IR source of constant size and temperature was presented to rattlesnakes (Crotalus atrox) at various distances (10-160 cm) from their snout. The snakes' responses were quantified by measuring distinct behavioural changes during stimulus presentation (head jerks, head fixed, freezing, rattling and tongue-flicking). The results revealed that C. atrox can detect an artificial IR stimulus resembling a mouse in temperature and size up to a distance of 100 cm, which corresponds to a radiation density of 3.35 x 10(-3) mW/cm2. These behavioural results reveal a 3.2 times higher sensitivity to IR radiation than earlier electrophysiological investigations.

Animals↗
PubMed2006

Olfactory conditioning of proboscis activity in Drosophila melanogaster.

Olfactory learning and memory processes in Drosophila have been well investigated with aversive conditioning, but appetitive conditioning has rarely been documented. Here, we report for the first time individual olfactory conditioning of proboscis activity in restrained Drosophila melanogaster. The protocol was adapted from those developed for proboscis extension conditioning in the honeybee Apis mellifera. After establishing a scale of small proboscis movements necessary to characterize responses to olfactory stimulation, we applied Pavlovian conditioning, with five trials consisting of paired presentation of a banana odour and a sucrose reward. Drosophila showed conditioned proboscis activity to the odour, with a twofold increase of percentage of responses after the first trial. No change occurred in flies experiencing unpaired presentations of the stimuli, confirming an associative basis for this form of olfactory learning. The adenylyl cyclase mutant rutabaga did not exhibit learning in this paradigm. This protocol generated at least a short-term memory of 15 min, but no significant associative memory was detected at 1 h. We also showed that learning performance was dependent on food motivation, by comparing flies subjected to different starvation regimes.

Adenylyl Cyclases↗
PubMed2006

Temperature affects interaction of visual and vibrational cues in parasitoid host location.

Parasitoid host location in nature is facilitated by simultaneously using different information sources. How multisensory orientation on the same spatial scale is influenced by environmental conditions is however poorly understood. Here we test whether changes in reliability of cues can cause parasitoids to alter multisensory orientation and to switch to cues that are more reliable under extreme temperatures. In the ichneumonid wasp Pimpla turionellae, multisensory use of thermally insensitive vision and thermally sensitive mechanosensory host location by vibrational sounding (echolocation on solid substrate) was investigated with choice experiments on plant-stem models under optimum temperature (18 degrees C), at high- (28 degrees C) and low-temperature limits (8 degrees C) of vibrational sounding. Temperature affected relative importance of vibrational sounding whereas visual orientation did not vary. At 18 degrees C, parasitoids used visual and vibrational cues with comparable relative importance. At 8 and 28 degrees C, the role of vibrational sounding in multisensory orientation was significantly reduced in line with decreased reliability. Wasps nearly exclusively chose visual cues at 8 degrees C. The parasitoids switch between cues and sensory systems depending on temperature. As overall precision of ovipositor insertions was not affected by temperature, the parasitoids fully compensate the loss of one cue provided another reliable cue is available on the same spatial scale.

Animals↗
PubMed2006

Psychometric function for nectar volume perception of a flower-visiting bat.

For foraging pollinators one aspect of floral quality is the volume of nectar available. Thus, nectar-feeding animals should be able to estimate volumes of received nectar. In this study, we determined the psychometric function for nectar volume discrimination of a Neotropical flower-visiting bat Glossophaga soricina. For this, we examined the ability of bats to discriminate between two nectar volumes in a two-alternative forced-choice paradigm. We used a Bayesian inference approach to determine psychometric functions. From the derived psychometric function we assessed the discrimination threshold at a value of 0.69. G. soricina could clearly distinguish between two volumes, when the difference between the two nectar volumes divided by their average exceeded this value. This indicates that bats possess a sense for the perception and discrimination of volumes of nectar that is better developed than in honeybees.

Animals↗