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PubMed2002

The delivery rate of dietary carbohydrates affects cognitive performance in both rats and humans.

RATIONALE: Glucose is the main metabolic fuel of the brain. The rate of glucose delivery from food to the bloodstream depends on the nature of carbohydrates in the diet, which can be summarized as the glycaemic index (GI). OBJECTIVES: To assess the benefit of a low versus high GI breakfast on cognitive performances within the following 4 h. METHODS: The influence of the GI of the breakfast on verbal memory of young adults was measured throughout the morning in parallel to the assessment of blood glucose levels. The learning abilities of rats performing an operant-conditioning test 3 h after a breakfast-like meal of various GI was also examined. RESULTS: A low GI rather than high GI diet improved memory in humans, especially in the late morning (150 and 210 min after breakfast). Similarly, rats displayed better learning performance 180 min after they were fed with a low rather than high GI diet. CONCLUSION: Although performances appeared to be only remotely related to blood glucose, our data provide evidence that a low GI breakfast allows better cognitive performances later in the morning.

Adult↗

PubMed2004

Attenuation of nicotine's discriminative stimulus effects in rats and its locomotor activity effects in mice by serotonergic 5-HT2A/2C receptor agonists.

RATIONALE: Reports have indicated that administration of nicotine inhibits, while withdrawal of chronically administered nicotine augments effects of serotonergic 5HT2A/2C agonists. OBJECTIVE: It was our objective to determine whether 5HT2A/2C agonists can modulate the discriminative stimulus effects of nicotine in rats or its locomotor activity effects in mice. METHODS: Adult male Sprague-Dawley rats were trained to discriminate 0.3 mg/kg nicotine base from saline in a two-lever, fixed-ratio (FR10), food-reinforced, operant-conditioning task during daily (Monday-Friday) 15-min experimental sessions. After characterizing a dose-response curve for nicotine, we tested the ability of the 5HT(2A/2C) agonists (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCL (DOI; 0.18-1.0 mg/kg) and 1-(4-bromo-2, 5-dimethoxyphenyl)-2-aminopropane (DOB; 0.1-1.0 mg/kg), the 5HT2C agonist 6-chloro-2-(1-piperazinyl)pyrazine hydrochloride (MK 212; 0.1 mg/kg-1.0 mg/kg), and the 5HT1A agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 0.01 mg/kg-1.0 mg/kg) to modulate nicotine's discriminative stimulus effects. After finding that DOI was able to attenuate the percentage nicotine lever responding (%NLR), we tested for it to also reverse nicotine's effects on locomotor activity in mice. RESULTS: The 5HT2A/2C agonists-in particular DOI-dose dependently attenuated %NLR. The effects of DOI were reversed by the 5HT2A/2C antagonist ketanserin. MK 212 and 8-OH-DPAT had irregular effects among rats and only reduced %NLR to below 50% levels at doses markedly suppressing responding. DOI also dose dependently blocked nicotine's acute rate-lowering locomotor activity effects. CONCLUSIONS: These results indicate that activation of serotonin 5HT2A/2C receptors can blunt the discriminative stimulus and locomotor activity effects of nicotine and presents the possibility that activation of these receptors might also be able to attenuate other effects of nicotine.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2005

Effect of a novel nicotinic receptor antagonist, N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide, on nicotine self-administration and hyperactivity in rats.

RATIONALE AND OBJECTIVE: Recent work has shown that the novel compound N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB) may selectively block nicotinic acetylcholine receptors involved in regulating dopamine release. The current experiments examined the acute effect of bPiDDB on nicotine self-administration, sucrose-maintained responding, and nicotine-induced changes in acute and sensitized locomotor activity. METHODS: Rats were first trained to respond for either nicotine (i.v.) or sucrose pellets using a standard two-lever operant conditioning procedure using a fixed ratio 5 schedule of reinforcement and were then pretreated with bPiDDB (0, 0.3, 1, or 3 mg kg(-1)) 15 min prior to the session. In separate experiments, rats were assessed for nicotine-induced changes in locomotor activity following pretreatment with bPiDDB (1 or 3 mg kg(-1)) or mecamylamine (1 mg kg(-1)); pretreatments were assessed with both acute and repeated nicotine (0.4 mg kg(-1)) treatment. RESULTS: Results showed that bPiDDB dose-dependently decreased nicotine self-administration, but not sucrose-maintained responding. In the locomotor experiments, bPiDDB attenuated the hyperactivity produced by acute and repeated nicotine; however, this effect was not robust compared to mecamylamine. In contrast to mecamylamine, bPiDDB did not block the initial hypoactivity produced by acute nicotine. CONCLUSION: Since bPiDDB decreased nicotine self-administration specifically, this novel nicotinic receptor antagonist may constitute a lead for the development of a clinically useful treatment for tobacco dependence.

Animals↗

PubMed2005

The psychopharmacology of impulsive behaviour in rats VIII: effects of amphetamine, methylphenidate, and other drugs on responding maintained by a fixed consecutive number avoidance schedule.

RATIONALE: Impulsive behaviour is a component of psychiatric disorders such as bipolar disorder, attention deficit hyperactivity disorder (ADHD), or personality disorders. Most experimental studies on impulsive behaviour punish impulsive choices by loss or delay of reward. In the present study, impulsive behaviour was punished by an explicitly aversive stimulus, using a novel fixed consecutive number (FCN) schedule of electric shock avoidance. OBJECTIVES: This study was conducted to demonstrate stable performance using the FCN avoidance procedure, and examine the effects of drugs previously shown to affect impulsive behaviour using a conventional FCN schedule. METHODS: First, rats were trained in the appetitive FCN procedure. Pressing the right lever in an operant conditioning chamber after having pressed the left lever at least six times delivered a food pellet (FCN6). Responses on the right lever before completing this ratio resulted in a time out and restarted the ratio. The rats were then switched to FCN avoidance. Responses on the right lever made before completion of the ratio also resulted in food delivery, but were accompanied by an electric shock. RESULTS: Chlordiazepoxide (10.0 mg/kg), ethanol (1.0 g/kg), and haloperidol (0.1 mg/kg) increased impulsive behaviour by reducing the number of left lever responses made before the right lever was pressed. Imipramine (1.0-10.0 mg/kg) and desipramine (1.0-10.0 mg/kg) had no effect on impulsive choice. Amphetamine (0.4 and 0.8 mg/kg) and methylphenidate (6.0 mg/kg) significantly increased the mean chain length, and the proportion of very long chains, indicative of reduced impulsivity, although this did not improve efficiency. CONCLUSIONS: The increases in impulsivity produced by chlordiazepoxide, ethanol, and haloperidol were similar to those under appetitive FCN schedules. In contrast, amphetamine and methylphenidate, by reducing impulsivity in the FCN avoidance, induced effects opposite to those observed in an appetitive FCN procedure. These results suggest that the therapeutic actions of stimulants, to reduce impulsive behaviour in ADHD, may arise in part by increasing the control of behaviour by aversive stimuli.

Animals↗

PubMed2006

Ethanol self-administration and reinstatement of ethanol-seeking behavior in Per1(Brdm1) mutant mice.

RATIONALE: Alcohol consumption shows circadian rhythmicity, i.e., alcohol preference and intake change with circadian time. Circadian rhythmicity is controlled by a biological clock, which has been shown to govern behavioral, physiological, and hormonal processes in synchronization with internal as well as external cues. Molecular components of the clock include circadian clock genes such as period (Per) 1, 2, and 3. Previously, our lab demonstrated the involvement of mouse Per1 (mPer1) and Per2 (mPer2) in modulating cocaine sensitization and reward. What is more, we investigated voluntary alcohol consumption in Per2 ( Brdm1 ) mice with the results suggesting a relationship between this circadian clock gene and ethanol consumption. Objective To further complement the mPer2 study, our lab proceeded to assess mPer1's possible role on alcohol intake using operant and free choice two bottle paradigms. METHODS: Using operant conditions, Per1 ( Brdm1 ) and wild type mice were trained to self-administer ethanol (10%) under a fixed ratio 1 (FR1) paradigm. This was ensued by a progressive ratio (PR) schedule. Furthermore, extinction sessions were introduced, followed by reinstatement measures of ethanol-seeking behavior. In another set of animals, the mice were exposed to voluntary long-term alcohol consumption, ensued by a 2-month deprivation phase, after which the alcohol deprivation effect (ADE) was measured. RESULTS: Mutant mice did not display a significantly divergent number of reinforced lever presses (FR1 and PR) than wild type animals. Furthermore, no significant differences between groups were obtained regarding reinstatement of ethanol-seeking behavior. Similar results were obtained in the two bottle free choice paradigm. Specifically, no genotype differences concerning consumption and preference were observed over a broad range of different ethanol concentrations. Moreover, after the deprivation phase, both groups exhibited significant ADEs, yet no genotype differences. CONCLUSIONS: Contrary to the mPer2 data, the present findings do not suggest a relationship between the circadian clock gene mPer1 and ethanol reinforcement, seeking, and relapse behavior.

Alcohol Drinking↗

PubMed2001

Behavioral reactions reflecting differential reward expectations in monkeys.

Learning theory emphasizes the importance of expectations in the control of instrumental action. This study investigated the variation of behavioral reactions toward different rewards as an expression of differential expectations of outcomes in primates. We employed several versions of two basic behavioral paradigms, the spatial delayed response task and the delayed reaction task. These tasks are commonly used in neurobiological studies of working memory, movement preparation, and event expectation involving the frontal cortex and basal ganglia. An initial visual instruction stimulus indicated to the animal which one of several food or liquid rewards would be delivered after each correct behavioral response, or whether or not a reward could be obtained. We measured the reaction times of the operantly conditioned arm movement necessary for obtaining the reward, and the durations of anticipatory licking prior to liquid reward delivery as a Pavlovian conditioned response. The results showed that both measures varied depending on the reward predicted by the initial instruction. Arm movements were performed with significantly shorter reaction times for foods or liquids that were more preferred by the animal than for less preferred ones. Still larger differences were observed between rewarded and unrewarded trials. An interesting effect was found in unrewarded trials, in which reaction times were significantly shorter when a highly preferred reward was delivered in the alternative rewarded trials of the same trial block as compared to a less preferred reward. Anticipatory licks preceding the reward were significantly longer when highly preferred rather than less preferred rewards, or no rewards, were predicted. These results demonstrate that behavioral reactions preceding rewards may vary depending on the predicted future reward and suggest that monkeys differentially expect particular outcomes in the presently investigated tasks.

Animals↗

PubMed2002

Olfactory discrimination of structurally similar alcohols by cockroaches.

The capability of the cockroach Periplaneta americana to discriminate odors of structurally similar aliphatic alcohols was studied by using an operant conditioning paradigm. Cockroaches were trained to discriminate three odors: one odor associated with sucrose solution (reward) and two odors associated with NaCl solution (non-reward). After training, their odor preferences were tested by counting the number of visits to each odor source. We tested the capability of cockroaches to discriminate (1) three normal aliphatic alcohols with different numbers of carbon (1-pentanol, 1-hexanol and 1-octanol), (2) three C6 aliphatic alcohols (1-hexanol, 2-hexanol and trans-2-hexen-1-ol), (3) binary mixtures of two of these three alcohols and their components, and (4) 1-hexanol solution of three different concentrations (1, 10 and 100 micro g micro l(-1)). Cockroaches exhibited higher preferences for the odors associated with reward in these tests, and we therefore conclude that cockroaches can discriminate these odors. However, discrimination of 1-hexanol and trans-2-hexen-1-ol and their binary mixture was imperfect, in that some statistical tests suggested significant level of discrimination but other tests did not. In addition, the cockroaches learned to associate a 1-hexanol solution of the highest or lowest concentration with sucrose reward but failed to learn to associate 1-hexanol of an intermediate concentration with reward.

1-Octanol↗

PubMed2004

Auditory sensitivity and frequency selectivity in greater spear-nosed bats suggest specializations for acoustic communication.

We investigated the relationship between auditory sensitivity, frequency selectivity, and the vocal repertoire of greater spear-nosed bats ( Phyllostomus hastatus). P. hastatus commonly emit three types of vocalizations: group-specific foraging calls that range from 6 to 11 kHz, low amplitude echolocation calls that sweep from 80 to 40 kHz, and infant isolation calls from 15 to 100 kHz. To determine if hearing in P. hastatus is differentially sensitive or selective to frequencies in these calls, we determined absolute thresholds and masked thresholds using an operant conditioning procedure. Both absolute and masked thresholds were lowest at 15 kHz, which corresponds with the peak energy of isolation calls. Auditory and masked thresholds were higher at sound frequencies used for group-specific foraging calls and echolocation calls. Isolation calls meet the requirements of individual signatures and facilitate parent-offspring recognition. Many bat species produce isolation calls with peak energy between 10 and 25 kHz, which corresponds with the frequency region of highest sensitivity in those species for which audiogram data are available. These findings suggest that selection for accurate offspring recognition exerts a strong influence on the sensory system of P. hastatus and likely on other species of group-living bats.

Acoustic Stimulation↗

PubMed2003

Vocal individual discrimination in Japanese monkeys.

The present study determines which features of the coo call are used by Japanese monkeys Macaca fuscata for vocal individual discrimination. First, two female Japanese monkeys were trained to discriminate conspecific individuals vocally, using an operant conditioning. Using as stimuli three unknown individuals with 30 calls per individual, the two monkeys succeeded in discriminating new call exemplars from the three stimulus individuals. A discriminant analysis performed on calls used as stimuli indicated that start frequency of the fundamental and call duration were variables that can differentiate individuals efficiently. Then, playbacks of acoustically modified signals were used to indicate which vocal features are used by monkeys for the individual discrimination. Stimuli signals containing modified pitch or duration, or filtered so as to keep only the fundamental component, were tested. Results indicated that Japanese monkeys use multiple acoustical cues to perform vocal individual discrimination, including at least pitch, call duration, and harmonics. However, harmonics seem to be less important for discrimination than pitch and call duration.

Acoustic Stimulation↗

PubMed1981

Posttraining changes in excitability of the commissural path-CA1 pyramidal cell synapse in the hippocampus of mice.

Mice were partially trained on a bar-press operant conditioning task on continuous reinforcement (CRF). The amplitude of population excitatory postsynaptic potentials (EPSPs) evoked by commissural stimulation of the Ca2 field of the dorsal hippocampus was found to significantly increase 1 h after training and then to decrease. This phenomenon was either not observed or much less evident in mice could not learn the task or which had already been trained on this task.

Animals↗

PubMed1981

Inhibition of intracranial self-stimulation in brain stem-transected cats--a proposed mechanism of aversive effects produced by brain stimulation.

Effects of intracranial self-stimulation of central 'punishment areas' were studied on an operant conditioning of vertical eye movements in the midpontine pretrigeminal cats as well as in the encéphale isolé cats. In 36 pretrigeminal cats, the ventromedial hypothalamus (VMH), basal amygdaloid nuclei (AMY), dorsal central gray (CG) of the midbrain and the thalamic nuclei such as the ventralis posteromedialis (VPM) and ventralis posterolateralis (VPL) were tested. No suppression of eye movements indicating a passive avoidance conditioning from stimulation of these 'punishment areas' was obtained in 92 electrode tip sites. In 49 encéphale isolé cats, stimulation of the VPM associated with contraction of the facial muscles, demonstrated a marked passive avoidance effect on the eye movements. After blocking both the trigeminal (5N) and facial nerves (7N), VPM stimulation no longer produced an increase of facial EMG activity and the suppressive effect on eye movements was abolished. Extracranial blockade of 7N alone, which induced facial muscle paralysis also showed similar effects. Bilateral blockade of cranial nerves from acoustic (8N) to hypoglossal (12N) nerves had no significant effect on the avoidance conditioning. The mass neural activity recorded from the 5N showed a marked increase of discharge by VPM stimulation which was reduced significantly after 7N blockade. These results may suggest a possibility that punishing effects of brain stimulation depend on feedback from the periphery (muscles, blood vessels and visceral organs), whereas reward effects essentially depend on neural circuitry confined within the forebrain above the rostral pons.

Amygdala↗

PubMed1983

Learning of fast and stable hand movement and cerebro-cerebellar interactions in the monkey.

Monkeys were trained to lift a lever by wrist extension in response to a light stimulus and changes of premovement cortical field potentials were observed during the training period with electrodes which had been chronically implanted in various cortical areas. The purpose of the study was to follow changes in potentials mediated by cerebro-cerebellar neuronal circuits as fast and stable hand movements were attained during later stages of motor learning. As compared to initial stages of an operantly conditioned movement in response to the light stimulus, further training shortened reaction times gradually over several weeks, and this was associated with gradual increases of premovement superficial thalamo-cortical (T-C) responses in the contralateral forelimb motor area. Since the T-C responses are known to depend at least in part on impulses from the neocerebellum, it is suggested that the neocerebellum--superficial T-C projection--motor cortex system is gradually recruited during motor learning and that this in turn contributes to fast and stable movements.

Animals↗

PubMed1993

Olfactory sensitivity of rats with transection of the lateral olfactory tract.

Rats with discrete transection of the lateral olfactory tract (LOT) were tested using operant conditioning and psychophysical methods for their amyl acetate intensity difference threshold and absolute detection threshold. Experimental rats performed as well as controls on the easiest problems of both threshold series but their intensity difference threshold was approximately 2.5 times as high as controls and their absolute detection threshold was approximately 2.25 orders of magnitude higher than controls. The deficit in sensitivity in both tests was related to the frontal level at which the tract was cut; rats with the most rostral transection had the greatest increase in threshold. The absolute detection threshold of rats with transection of the LOT was increased to that of normal human subjects tested with the same apparatus.

Animals↗

PubMed1994

Clozapine attenuates the discriminative stimulus properties of (-)-nicotine.

Rats were trained to discriminate 1.9 mumol/kg (-)-nicotine (0.3 mg/kg) from saline in a standard two-bar operant conditioning paradigm with food reinforcement. The effect of neuronal nicotinic acetylcholine receptor (nAChR) agonists and antagonists were verified, and the participation of dopaminergic receptors subtypes in the expression of the (-)-nicotine cue was investigated with cis-flupentixol (D1-D2 antagonist), haloperidol (D2 antagonist) and clozapine (D4 antagonist). The stereoselectivity of the behavioral response was indicated by the 10-fold less sensitivity to (+)-nicotine in (-)-nicotine-trained rats. (+/-)-Anabasine and (-)-cytisine exhibited partial agonist profiles at the 1.9 mumol/kg dose while (-)-lobeline was devoid of any effect in doses up to 19 mumol/kg. (-)-Lobeline did not show antagonist properties in this paradigm. The nicotinic channel blockers mecamylamine, chlorisondamine and hexamethonium were inactive on their own but mecamylamine and chlorisondamine were able to block the effect of (-)-nicotine. Clozapine attenuated the (-)-nicotine cue while cis-flupentixol and haloperidol were ineffective. Similar doses of cis-flupentixol significantly blocked the locomotor stimulant effect of (-)-nicotine in rats indicating that blockade of dopaminergic receptors was achieved at the doses used in the drug discrimination studies. These data suggest that the discriminative stimulus properties of (-)-nicotine are mediated through neuronal nAChRs and involves the activation of dopaminergic receptors of the D4 subtype.

Alkaloids↗

PubMed1984

Time-dependent effects of posttraining intrahippocampal injections of corticosterone on retention of appetitive learning tasks in mice.

In previous studies we suggested that corticosterone may modulate hippocampal functioning during memory formation. To test this assumption, we studied the effects of posttrial administration of corticosterone (1 microgram) injected bilaterally in the hippocampus. The treatment was applied at different time intervals after the learning session and the retention session took place 24 h later. Using appetitive operant conditioning tasks in a Skinner box, we found that the posttrial treatment 1) did not affect the retention of a continuously reinforced schedule, 2) improved the retention of a successive discrimination learning task, and 3) was still effective when given 3 h after the acquisition of this task, but not after 6 h. Taken together, the results suggest that corticosterone modulates the hippocampal mechanisms involved in behavioral suppression during memory formation.

Animals↗

PubMed1990

Characterisation of the discriminative stimulus properties of flumazenil.

Rats were trained to discriminate flumazenil (15 mg/kg i.p.) from vehicle in a two-lever, food-reinforced, operant conditioning procedure. Substitution tests were performed with a wide dose range of flumazenil and of several benzodiazepines and non-benzodiazepine compounds possessing behavioural effects similar to or opposite to those of benzodiazepine agonists. The results indicate that low doses of flumazenil have behavioural effects, that the flumazenil cue has a low degree of specificity and is most strongly related to the stimulus properties of benzodiazepines.

Animals↗

PubMed1975

Dissociation of operant and consummatory responses by trigeminal deafferentation in the pigeon.

Section of peripheral sensory branches of the pigeon's trigeminal nerve abolishes or decreases feeding responses made in an operant conditioning situation without directly impairing performance of an operant key-pecking response reinforced with food. The results are discussed in relation to previous studies of trigeminal function in the pigeon and suggest the possibility of dissociating neural mechanisms underlying feeding behavior and operant conditioning in this species.

Animals↗

PubMed1975

Ability of the pig to distinguish between conspecific urine samples using olfaction.

In two female pigs it has been shown using operant conditioning techniques in which the animals pushed panels with their snouts in order to obtain food, that they could distinguish between the oder from urine samples taken from other pigs. In the discrimination task, the pigs faced two panels and a tube adjacent to one of the panels emitted urine odor used as the positive discriminative stimulus while another tube adjacent to the other panel emitted the negative discriminative stimulus consisting of odor from another urine sample. Only presses on the panel associated with the positive stimulus were reinforced on a fixed ratio schedule of 6. Both positive and negative discrimination stimuli were presented simultaneously. After each reinforcement the position of the positive and negative odor stimuli was varied according to the Gellerman series. When fully trained, the pigs made very few responses on the incorrect panel.

Animals↗