A mathematical analysis on the biological zero problem in laser Doppler flowmetry

Whilst neurons within the lateral hypothalamus are well known to be responsive to the presentation of previously learned associative stimuli, the consolidation of a Pavlovian association is thought to depend in large part upon other brain regions, including the amygdala. The present study addressed this assumption directly, by examining the effect of post-session infusions of sulpiride within the lateral hypothalamus upon the acquisition of a conditioned approach response in an appetitive differential conditioning task. Subjects were exposed to an initially neutral stimulus (CS+), which immediately preceded the availability of a 10% sucrose reward (US). A second, control stimulus (CS ) was also presented. but never in close temporal proximity to the US. The number and duration of alcove approaches were recorded. Immediately following each training session, subjects were infused bilaterally with sulpiride (0, 0.5, 5 microg) in the vicinity of the perifornical region of the lateral hypothalamus. Sulpiride dose-dependently enhanced the rate of acquisition of a conditioned approach response to presentation of the CS+, but was without affect upon approach behaviour during CS(-) or US presentations. Thus, 0.5 microg sulpiride facilitated at an early stage (session 2 onwards) the number of alcove approaches to the CS+, while 5 microg sulpiride enhanced to a greater extent the duration of conditioned approach, particularly during later sessions. A subsequent locomotor test using 0.5 mg/kg d-amphetamine indicated that repeated infusions of the higher dose sulpiride (5 microg), but not the lower dose (0.5 microg), resulted in behavioural sensitisation to administration of the psychomotor stimulant. Acquisition of a novel conditioned instrumental response was not affected by previous exposure to sulpiride. These data suggest that dopamine-sensitive neurons within the lateral hypothalamus may play a significant role in the acquisition of appetitive Pavlovian associations.     

Acquired appetitive responding to intravenous nicotine reflects a Pavlovian conditioned association.

Recent research examining Pavlovian appetitive conditioning has extended the associative properties of nicotine from the unconditioned stimulus or reward to include the role of a conditional stimulus (CS), capable of acquiring the ability to evoke a conditioned response. To date, published research has used presession extravascular injections to examine nicotine as a contextual CS in that appetitive Pavlovian drug discrimination task. Two studies in the current research examined whether a nicotine CS can function discretely, multiple times within a session using passive iv infusions. In Experiment 1, rats readily acquired a discrimination in conditioned responding between nicotine and saline infusions when nicotine was selectively paired with sucrose presentations. In Experiment 2, rats were either trained with nicotine paired with sucrose or explicitly unpaired with sucrose. The results showed that rats trained with explicitly unpaired nicotine and sucrose did not increase dipper entries after the infusions. Nicotine was required to be reliably paired with sucrose for control of conditioned responding to develop. Implications of these findings are discussed in relation to tobacco addiction, learning theory, and pharmacology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intracerebroventricular ethanol-induced conditioned place preferences are prevented by fluphenazine infusions into the nucleus accumbens of rats.

The rewarding properties of centrally administered ethanol (EtOH) were examined using a conditioned place preference (CPP) test. Male rats subjected to bilateral intracerebroventricular (icv) infusions of EtOH (0-240 nmol) produced a dose-dependent preference for the drug-paired environment that was potentiated by concurrent intravenous (iv) administration of heroin (0.025 mg/kg). The role of mesolimbic dopamine (DA) pathways in the development of EtOH reward was then examined by challenging EtOH-treated rats with bilateral intra-accumbens shell applications of a DA receptor antagonist. Fluphenazine (10 or 50 μg/side), infused immediately prior to daily place conditioning trials, was found to reliably attenuate the development of CPPs produced by icv EtOH administration. When fluphenazine was administered into the nucleus accumbens shell prior to the final test trial only (i.e., in already conditioned rats), intra-accumbens shell DA receptor blockade was found to prevent the expression of CPPs produced by icv EtOH. In summary, rats form reliable learned preferences for EtOH-paired locations (CPPs) that are potentiated by iv heroin and whose acquisition and expression rely on intact DA functionality within the nucleus accumbens. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of selective excitotoxic lesions of the nucleus accumbens core, anterior cingulate cortex, and central nucleus of the amygdala on autoshaping performance in rats.

The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an impaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS + significantly less often than controls, failing to discriminate between the CS + and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of excitotoxic lesions of the central amygdaloid nucleus on the potentiation of reward-related stimuli by intra-accumbens amphetamine.

The present study examined the effects of lesions of the central nucleus of the amygdala (CeA) on the acquisition of a new response with conditioned reinforcement (CR) and its potentiation by intra-accumbens infusions of d-amphetamine (1, 3, 10, and 20 μg/μl). Rats were trained to associate a light-plus-noise compound stimulus with the availability of a sucrose solution before receiving both bilateral ibotenic acid lesions of the CeA and cannulas implanted above the nucleus accumbens. Lesions of the central nucleus did not impair the performance of positively reinforced discriminated approach, nor did they impair the acquisition of a new response with conditioned reinforcement. However, the potentiation of responding with CR following intra-accumbens amphetamine was blocked in lesioned animals. These results are discussed in terms of the possible interactions between associative mechanisms in the amygdala and the mesolimbic dopamine projection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Double dissociation of the behavioural effects of R(+) 7-OH-DPAT infusions in the central and basolateral amygdala nuclei upon Pavlovian and instrumental conditioned appetitive behaviours

Dopaminergic cell bodies located within the ventral mesencephalon innervate the amygdaloid complex, a region critically involved in the attribution of affective significance to environmental stimuli. Recently, we have shown that post-session intra-amygdala administration of a D3 dopamine receptor agonist enhances selectively the acquisition of an appetitive conditioned response. In the present study, we have investigated the potential involvement of the central nucleus and the basolateral nuclei of the amygdala in mediating this effect. Thus, rats were trained to associate an arbitrary stimulus (CS+) with the availability of 10% sucrose reward. Post-session infusions of the D3 receptor-preferring agonist, R(+) 7-OH-DPAT, were made into either the central nucleus or basolateral nuclei. Acquisition of a conditioned approach response was enhanced by R(+) 7-OH-DPAT infusions within the central nucleus, but not within the basolateral nuclei. Drug infusions into either region failed to affect approach behaviour elicited by presentation of a control stimulus (CS-), explicitly unpaired with sucrose reward. The effects of pre-test infusions of R(+) 7-OH-DPAT on the instrumental properties of the stimuli were then determined. Rats were presented with two novel levers, depression of one lever resulted in presentation of the CS+, while presentation of the CS- was contingent upon depression of the other lever. Rates of response upon each lever as well as the ability of the conditioned stimuli subsequently to elicit conditioned approach behaviour were recorded. Data revealed a double dissociation of the effects of R(+) 7-OH-DPAT on the expression of the Pavlovian and instrumental properties of the reward-related stimulus. Thus, within the central nucleus R(+) 7-OH-DPAT dose-dependently attenuated expression of the conditioned approach response, but had no effect upon instrumental responding maintained by the conditioned reward. In contrast, within the basolateral nuclei, R(+) 7-OH-DPAT had no effect upon expression of conditioned approach behaviour, but abolished selectively the ability of the reward-associated stimulus to support the acquisition of a novel instrumental response. Hence, these data indicate that distinct regions of the amygdaloid complex process distinct aspects of conditioned appetitive behaviours.     

Disruption of Pavlovian contextual conditioning by excitotoxic lesions of the nucleus accumbens core.

Nucleus accumbens (NAcc) core lesions were performed either before or after Pavlovian aversive conditioning. NAcc core lesions had no effect on discrete-cue or contextual conditioned freezing during acquisition. During retention testing, neither pre- nor posttraining lesions had any effect on conditioned freezing to the discrete cue. However, pretraining lesions resulted in a profound impairment of contextual conditioned freezing in a retention test, and posttraining lesions resulted in a smaller impairment. NAcc core lesions had no effect on sensory or motor processes, as measured by shock reactivity and spontaneous locomotor activity. These results suggest that during acquisition, processes independent of the NAcc core mediate contextual conditioned freezing, but that the NAcc is implicated in the retention of this aversive memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Basal forebrain cholinergic lesions enhance conditioned approach responses to stimuli predictive of food

This study examined the effects of lesions to different neuronal populations within the basal forebrain on reward-related learning. Rats received bilateral alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or quinolinate lesions that preferentially destroy the cholinergic nucleus basalis magnocellularis (NBM) or noncholinergic ventral pallidal neurons, respectively. Both lesions enhanced conditioned approach responses to stimuli predictive of food but did not increase the locomotor stimulating effect of d-amphetamine. Although both lesions disrupted the discriminative control over behavior by a conditioned stimulus, they did not impair the subsequent acquisition of instrumental responding with conditioned reinforcement (CR). Indeed, both lesions were associated with an increased responding with CR following intra-accumbens infusions of d-amphetamine (0, 1, 3, 10, and 20 microg). Quinolinate lesions also increased responses on an inactive control lever. Neither lesion altered consummatory responses to food or sucrose. Results suggest that NBM lesions may disrupt the balance between cortical and subcortical dopamine levels, and/or produce a deficit in attentional mechanisms that is manifested as increased responding to specific stimuli.     

Normal conditioning inhibition and extinction of freezing and fear-potentiated startle following electrolytic lesions of medial prefrontal cortex in rats.

The authors investigated the role of medial prefrontal cortex (mPFC) in the inhibition of conditioned fear in rats using both Pavlovian extinction and conditioned inhibition paradigms. In Experiment 1, lesions of ventral mPFC did not interfere with conditioned inhibition of the fear-potentiated startle response. In Experiment 2, lesions made after acquisition of fear conditioning did not retard extinction of fear to a visual conditioned stimulus (CS) and did not impair "reinstatement" of fear after unsignaled presentations of the unconditioned stimulus. In Experiment 3, lesions made before fear conditioning did not retard extinction of fear-potentiated startle or freezing to an auditory CS. In both Experiments 2 and 3, extinction of fear to contextual cues was also unaffected by the lesions. These results indicate that ventral mPFC is not essential for the inhibition of fear under a variety of circumstances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned changes in dopamine oxidation currents in the nucleus accumbens of rats by stimuli paired with self-administration or yoked-administration of d-amphetamine

In vivo chronoamperometry was used to monitor changes in dopamine oxidation currents corresponding to dopamine efflux in the nucleus accumbens of rats after presentation of a conditioned light stimulus repeatedly paired with either yoked- or self-administered intravenous injections of the psychostimulant d-amphetamine. Daily conditioning trials began with a non-contingent drug injection, paired with a conditioned stimulus consisting of a 5 s flashing light and 30 s lights out, after which a house light was illuminated during the 3 h session, signalling drug availability. Each subsequent injection of d-amphetamine was paired with the conditioned stimulus. Electrochemical measures were taken on conditioning trials 4-7, and on each trial, intravenous d-amphetamine (0.25 mg/kg per injection) self-administration produced a significant maximal increase in mean dopamine oxidation currents of approximately 8 nA above baseline. Dopamine oxidation currents in rats receiving yoked d-amphetamine were approximately 5 nA above baseline by the fourth day of drug administration and reached approximately 8 nA on the seventh and final day of drug administration. On day 9 the first presentation of the vehicle injection and conditioned stimulus, in combination with illumination of the house lights, induced an immediate increase in nucleus accumbens dopamine oxidation currents in all rats that had previously received d-amphetamine. Subsequent presentations of the conditioned stimulus at 30 min intervals induced further increases in extracellular dopamine oxidation currents in both drug-treated groups. By the end of the 3 h session, both groups had similar maximal conditioned increases in dopamine oxidation currents of approximately 6 nA. These data are discussed with relation to the neurochemistry of drug craving.     

Temporal Coding in Conditioned Inhibition: Analysis of Associative Structure of Inhibition.

Two experiments with rats as subjects were conducted to investigate the associative structure of temporal control of conditioned inhibition through posttraining manipulation of the training excitor-unconditioned stimulus (US) temporal relationship. Experiment 1 found that following simultaneous Pavlovian inhibition training (i.e., A → US/XA-no US) in which a conditioned stimulus (CS A) was established as a delay excitor, maximal inhibition was observed on a summation test when CS X was compounded with a delay transfer CS. Furthermore, posttraining shifts in the A-US temporal relationship from delay to trace resulted in maximal inhibition of a trace transfer CS. Experiment 2 found complementary results to Experiment 1 with an A-US posttraining shift from serial to simultaneous. These results suggest that temporal control of inhibition is mediated by the training excitor-US temporal relationship. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute alcohol intoxication disrupts brightness but not olfactory conditioning in preweanling rats.

The present experiments tested the effect of acute alcohol administration on Pavlovian conditioning of 21-day-old rats using conditioned stimuli of two different sensory modalities—olfaction, an early developing sensory capacity functional at birth, and vision, a later developing sensory system not becoming functional until approximately 15 days of age. Conditioning and testing were conducted between 30 and 60 min following gastric intubation with either physiological saline or a mildly intoxicating alcohol dose (1.5 g/kg body weight). Brain alcohol levels were observed to remain at a peak and stable concentration during this period (Experiment 1). Alcohol impaired acquisition or expression of conditioned aversions to a visual cue paired with footshock when presented either as a single-element conditioned stimulus or as part of an odor/visual compound stimulus (Experiment 2), but it had no discernible effect on conditioned aversions to an olfactory stimulus that had similarly been paired with footshock (Experiments 2 and 3). The results suggest that alcohol may impair some aspects of learning but spare others, depending perhaps on the particular sensory modality to be conditioned. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiation of the acoustic startle response by a conditioned stimulus paired with acoustic startle stimulus in rats.

The hypothesis that the standard acoustic startle habituation paradigm contains the elements of Pavlovian fear conditioning was tested. In a potentiated startle response paradigm, a startle stimulus and a light conditioned stimulus (CS) were paired. A startle stimulus then was tested alone or following the CS. Freezing behavior was measured to index conditioned fear. The startle response was potentiated on CS trials, and rats froze more in CS than in non-CS periods. In Experiment 1, response to a previously habituated, weak startle stimulus was potentiated. In Experiment 2, response to the same stimulus used as the unconditioned stimulus (US) in training was potentiated. This CS-potentiated response retarded the course of response decrements over training sessions as compared with an explicitly unpaired control group. Conditioned fear is a standard feature of this habituation paradigm, serves to potentiate the startle response, and provides an associative dimension lacking in the habituation process per se. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of the acquisition of the rabbit eyeblink conditioned response by conditioned contextual stimuli.

Three experiments were conducted to ask if conditioned emotional responses (CERs) controlled by contextual cues modulate the acquisition of eyelid conditioned responses (CRs) to discrete conditioned stimuli (CSs). Experiment 1 showed that 30-s auditory stimuli that were paired with aversive shocks to one paraorbital region or the other controlled discriminated CERs, as measured by potentiation of a startle response. In Experiments 2 and 3, similarly trained 30-s stimuli served as contexts in which 1,050-ms CSs were paired with a paraorbital unconditioned stimulus (US). Reinforced contexts both impaired (Experiments 2A and 2B) and facilitated (Experiment 3B) acquisition of the eyeblink CR, depending on the locus of the USs involved. The data are consistent with the interpretation that CERs controlled by contextual cues facilitate CR acquisition, but do so in the face of blocking effects of CR tendencies also conditioned to the contextual cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amount of training affects associatively-activated event representation

The effects of variations in the amount of training on behavioral plasticity were examined in three experiments that used appetitive Pavlovian conditioning procedures with rats. In experiments 1 and 2, an auditory conditioned stimulus (CS) substituted for a food unconditioned stimulus (US) in the acquisition of new learning about the food US after small numbers of CS-US pairings, but not after larger numbers of pairings. After limited exposure to the relation between the auditory CS and food, pairings of the CS with the toxin LiCl, in the absence of food, were sufficient to establish an aversion to the food US that was previously paired with that CS. This CS-mediated learning did not occur after more extensive exposure to the CS-food relation. In contrast, in experiment 3. mediated performance of previously-established conditioned responding was unaffected by the number of CS-US pairings used to establish that performance. Conditioned responding to the auditory CS remained sensitive to post-training devaluation of the food US regardless of the amount of initial CS-US training. Implications of these results for the investigations of cortical and other brain mechanisms of behavioral plasticity are discussed.     

A Role for CS-US Contingency in Pavlovian Conditioning.

Two experiments evaluated the role of conditioned stimulus-unconditioned stimulus (CS-US) contingency in appetitive Pavlovian conditioning in rats. In both experiments, some groups received a positively contingent CS signaling an increased likelihood of the US relative to the absence of the CS. These groups were compared with control treatments in which the likelihood of the US was the same in the presence and absence of the CS. A trial marker served as a trial context. Experiment 1 found contingency sensitivity. There was a reciprocal relationship between responding to the CS and the trial marker. Experiment 2 showed that this result was not stimulus or response specific. These results are consistent with associative explanations and the idea that rats are sensitive to CS-US contingency. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stress enhances excitatory trace eyeblink conditioning and opposes acquisition of inhibitory conditioning

Exposure to a brief, stressful event is reported to facilitate classical eyeblink conditioning in the male rat (Rattus norvegicus) by use of a delay paradigm in which the conditioned stimulus (CS) and unconditioned stimulus (US) overlap and coterminate. This study examined the effects of stress on trace conditioning, a task in which the CS and US were separated by 500 ms. Experiment 1 showed that exposure to brief (1 s), low-intensity (1 mA) tailshocks facilitated acquisition 24 hr later. Experiment 2 showed that stressor exposure did not affect retention or extinction of trace conditioning in rats that were stressed after acquisition. Experiment 3 showed that exposure to the same stressor opposed acquisition of inhibitory conditioning. These results suggest that exposure to a stressful event persistently facilitates acquisition of trace conditioning and enhances a bias toward acquiring positive versus negative associations.     

Muscarinic receptor antagonism of the nucleus accumbens core causes avoidance to flavor and spatial cues.

Pharmacological blockade of muscarinic receptors in the nucleus accumbens reduces food intake and instrumental behaviors that are reinforced by food delivery. Nucleus accumbens muscarinic antagonism may specifically suppress the hedonic or reinforcing effects of food, thus blocking its capacity to direct behavior. Alternatively, muscarinic receptor blockade may cause a negative hedonic state that interferes with appetitive learning and food intake. In these experiments, rats received infusions of scopolamine methyl bromide (10 μg/0.5 μl) into the nucleus accumbens core, following exposure to a novel flavor of liquid diet (Experiment 1) or prior to being placed into a place preference apparatus (Experiment 2). In both experiments, nucleus accumbens muscarinic receptor antagonism caused subsequent avoidance of the paired cue (flavor or spatial location). This effect was specific to cholinergic manipulation; no conditioned taste avoidance was observed after pairing the novel flavor with nucleus accumbens core antagonism of N-methyl-D-aspartate, dopamine D?, or opioid receptors (Experiment 3). These experiments confirm previous reports of a critical role for striatal acetylcholine in modulating goal-directed behaviors, but suggest caution when interpreting behavioral effects of pharmacological manipulation of striatal acetylcholine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparator mechanisms and conditioned inhibition: Conditioned stimulus preexposure disrupts Pavlovian conditioned inhibition but not explicitly unpaired inhibition.

Three conditioned lick-suppression experiments with rats examined the effects of pretraining exposure to the conditioned stimulus (CS) on behavior indicative of conditioned inhibition. After CS-preexposure treatment, subjects received either Pavlovian conditioned inhibition training or explicitly impaired inhibition training with the preexposed CS. The inhibitory status of the CS was then assessed with a retardation (Experiment 1) or a summation (Experiment 2) test. Experiment 3 controlled for the unconditioned stimulus-preexposure effect being a potential confound in Experiments 1 and 2. As predicted by the comparator hypothesis (R. R. Miller & L. D. Matzel, 1988), the CS–context association that developed during the CS-preexposure phase disrupted the expression of Pavlovian conditioned inhibition but not the expression of explicitly impaired inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A differential involvement of the shell and core subterritories of the nucleus accumbens of the rats in memory processes.

The role of the core and the shell subterritories of the nucleus accumbens in conditioned freezing and spatial learning was investigated by means of selective N-methyl-D-aspartate lesions. Shell-lesioned rats showed reduced conditioned freezing to context and a tendency toward reduced freezing to the discrete stimulus compared with controls. However, lesions of the core did not modify the freezing response either to the context or to the discrete stimuli. Although spatial memory, as assessed by a water-maze paradigm, was not disrupted by the lesions, in a 4-arm baited, 4-arm unbaited radial-arm maze paradigm, the shell-lesioned rats showed selective deficits in working memory, but not in reference memory. In contrast, core-lesioned rats showed no memory deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)