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PubMed2000

Comparative neuropsychology of the dual brain: a stroll through animals' left and right perceptual worlds.

Perceptual asymmetries in humans typically manifest themselves under quite unnatural settings (e.g., tachistoscopic viewing and dichotic listening) and this has put into question their real biological significance. In animals with laterally placed eyes, however, perceptual asymmetries are ubiquitous in the normal, everyday behavior, as revealed by the differential use of the lateral visual field of the left and right eye in a variety of tasks. Data are presented showing how preferential use of the left and right eyes influences visual discrimination learning and detour behavior in chicks; similarities with detour tests performed in fish and evidence for asymmetries in eye use in animals with larger binocular overlap (e.g., anuran amphibians) are discussed. Implications of these perceptual asymmetries on the formation and fate of memory traces are put forward, with examples from unihemispheric sleep and lateralization of spatial memory in chicks. Finally, speculations about the evolutionary origins and possible adaptive advantages of perceptual asymmetries in vertebrates are presented.

Animals↗
PubMed1998

Developmental changes in the effect of dimensional salience on the discriminability of object relations.

Two experiments explored three issues regarding the nature of perceptual development in 5- and 10-year-old children and adults: (a) the role of featural discriminability, (b) the facilitatory role of identity relations, and (c) the role of salience in a task context designed to minimize the likelihood of attention-switching between dimensions during perceptual processing. In Experiment 1, perceptual salience for size and achromatic color dimensions was determined for each participant based on their best-fitting triad classification task response pattern. These same persons participated in Experiment 2, which employed a speeded visual discrimination task. The primary finding was that preassessed salience significantly influenced the 5-year-olds' ability to discriminate between two objects, while salience did not affect 10-year-olds' or adults' response times. The results of both experiments support Odom & Cook's (1992) differential-sensitivity view of perceptual development, but these data contribute important information by showing that salience effects in perceptual processing occur even when the observer is selectively attending to a particular dimension, likely during early component processes prior to classification.

Adult↗
PubMed1985

Enhanced sensory convergence to the visual cortex in the rodless (rd/rd) mouse.

The rd/rd mutation provokes a specific degeneration of the photoreceptive cells in the mouse retina, without affecting other neuronal elements. This degeneration starts 8 to 10 days after birth. Discriminative learning experiments have shown the degenerated retina to remain light-sensitive, the sensitivity being reduced to 10(-5) of normal with a peak still at 500 nm. An ontogenetic study showed a progressive vanishing of visual potentials (electroretinogram and visual evoked potentials) during the third week of life. Potentials of auditory origin, which can be recorded from the visual cortex in normal mice, were found to be clearly facilitated by the absence of the visual input either because of retinal degeneration in rd mouse or provoked by enucleation at birth.

Animals↗
PubMed1988

A comparison of the stimulus effects of codeine in rhesus monkeys under the contingencies of a two lever discrimination task and a cross self-administration paradigm: tests of generalization to pentazocine, buprenorphine, tilidine, and different doses of codeine.

The stimulus effects of codeine were assessed in three monkeys trained to perform first under the contingencies of a cross self-administration paradigm and then under a two lever discrimination task. Codeine-trained monkeys generalized to pentazocine, buprenorphine, and codeine under both procedures in doses different from the training dose. Codeine-trained monkeys did not generalize to tilidine. These results indicate that monkeys do not behave in a qualitatively different way when presented with the study drugs under both contingencies. However, there were marked quantitative differences between the generalization effects of doses of pentazocine, buprenorphine, and codeine to doses other than that used in training between the two paradigms. Much higher doses of codeine and pentazocine, but not of buprenorphine, were necessary for inducing generalization effects in the two lever task than in the cross self-administration procedure. The possible reasons for these quantitative differences are discussed. It is concluded that the cross self-administration procedure is more sensitive for the assessment of opioid-like stimulus properties of drugs than the two lever discrimination task.

Animals↗
PubMed1987

Effects of single or multiple choice trials per session on drug discrimination performance.

Drug discrimination procedures typically provide for multiple choice opportunities per training session. This practice allows non-drug cues (presence or absence of reinforcement) to mediate choice behavior during that portion of the session following the initial choice. In this experiment, rats were trained to discriminate 1.0 mg/kg cyclazocine from saline using a novel procedure that employed a single-choice trial per training session. Drug discrimination acquisition and generalization were compared to those of rats given discrimination training with 30 choice trials per session. The one-trial procedure yielded stable and reliable acquisition but more slowly than did the multiple trials procedure. The one-trial procedure produced longer first trial choice latencies and enhanced the tendency for subjects to respond on both choice levers during the first trial. The cyclazocine generalization functions were comparable, but the one-trial subjects more often responded on both choice levers, particularly when administered intermediate test doses of cyclazocine. Control of choice behavior by the reinforcer cue was evaluated on a mid-session cue reversal test. Multiple-trial subjects persisted in responding on the saline level following a mid-session injection of cyclazocine, whereas one-trial subjects shifted to the cyclazocine-appropriate lever.

Animals↗
PubMed1988

Effects of d-amphetamine, morphine, naloxone, and drug combinations on visual discrimination in rats.

The effects of d-amphetamine, morphine, and naloxone on visual discrimination were investigated using a two-choice discrete-trial procedure in which rats were trained to discriminate the position of a lightflash. Morphine (0.3-5.6 mg/kg) but not amphetamine (0.1-1.0 mg/kg) caused a significant dose-dependent disruption in discriminative performance. Both amphetamine and morphine increased response latencies. Naloxone (1.0 mg/kg) prevented the disruption of any aspect of performance by up to 100 mg/kg morphine. Performance after naloxone/amphetamine co-administration was not significantly different from that observed after amphetamine alone. Naloxone alone (0.3-10 mg/kg) had no effect on discrimination, spatial bias or response latencies. These results suggest that morphine and amphetamine affect different components of discrimination performance.

Animals↗
PubMed1986

The effects of compounds related to gamma-aminobutyrate and benzodiazepine receptors on behavioural responses to anxiogenic stimuli in the rat: extinction and successive discrimination.

In a first set of experiments rats were trained to run in a straight alley for food reward on a continuous reinforcement schedule and the running response was then extinguished. On the last 2 days of training and daily throughout extinction different groups of animals were injected IP with saline, 5 mg/kg chlordiazepoxide, 0.75 mg/kg picrotoxin, chlordiazepoxide + picrotoxin, chlordiazepoxide + 1.5 mg/kg bicuculline, 0.00125 or 0.25 mg/kg muscimol, 1 mg/kg baclofen, chlordiazepoxide + baclofen, or 0.00125 mg/kg muscimol + baclofen. Chlordiazepoxide increased resistance to extinction, a well-known anxiolytic effect. This effect was blocked by both picrotoxin and bicuculline. Picrotoxin on its own reduced resistance to extinction (an anxiogenic-like effect). Whether given alone or in combination with other drugs, muscimol and baclofen had no effect. In a second set of experiments rats were trained in a successive operant discrimination (signalled by a flashing or steady light) between components in which sucrose reward was available on a variable-interval schedule for barpressing and components in which no reward was given. Chlordiazepoxide at 10 mg/kg increased responding in both rewarded and nonrewarded components, but more in the latter than could be accounted for by change in the former. This effect is as expected with an anxiolytic drug. It was not altered by administration of bicuculline at 1.5 or 1.75 mg/kg; at 2 mg/kg bicuculline acted synergistically with chlordiazepoxide. Picrotoxin (1 and 1.5 mg/kg) also acted synergistically with chlordiazepoxide, enhancing the latter's rate-increasing effects, but only during rewarded components. Neither muscimol (0.00125 and 0.25 mg/kg) nor baclofen (0.01 mg/kg) affected response rates, whether given alone or in combination. However, baclofen in a dose of 1 mg/kg, provided it was given to rats also injected with muscimol (0.00125 or 0.25 mg/kg) at other times, significantly reduced responding during nonrewarded components (an apparently anxiogenic effect). The results of the two sets of experiments are discussed in relation to the hypothesis that anxiolytic drugs affect behaviour by increasing GABAergic inhibition.

Animals↗
PubMed1986

Effects of training dose on discrimination and cross-generalization of chlordiazepoxide, pentobarbital and ethanol in the rat.

Six groups of rats (N = 8), trained to discriminate chlordiazepoxide (5 or 20 mg/kg), pentobarbital (5 or 15 mg/kg) or ethanol (750 or 1500 mg/kg) from saline in a two-lever food-reinforced procedure, were tested for stimulus generalization with the three drugs. Training drug, but not training dose, affected the extent of generalization to a test drug; symmetrical generalization between chlordiazepoxide and pentobarbital and asymmetrical generalization between chlordiazepoxide and ethanol and between pentobarbital and ethanol was observed. Training dose level affected slope and ED50 of the generalization gradients of training drugs and substitution drugs, discriminative performance, response bias and threshold dose for response suppression. Indices of lever selection and percentage drug-appropriate lever responses yielded similar generalization maxima, slopes and ED50S. The potency of chlordiazepoxide relative to the potency of pentobarbital to induce drug stimulus generalization varied across the experimental groups. The results indicate differences between the discriminative effects of chlordiazepoxide, pentobarbital and ethanol. It is suggested that the discriminative effects of chlordiazepoxide, pentobarbital and ethanol are not based on their response rate modulating effects and that training dose is not a determinant for the extent of cross-generalization between these compounds.

Animals↗
PubMed1986

Discriminative stimulus properties of the serotonin agonist MK 212.

In an attempt to clarify the role of 5-hydroxytryptamine (5-HT) in the discriminative stimulus properties of MK 212 (6-chloro-2[1-piperazinyl]pyrazine), male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg of this compound from saline. While the putative 5-HT agonists fenfluramine and m-chlorophenylpiperazine (MCPP) mimicked MK 212 in a dose-related manner, d-lysergic acid diethylamide (LSD), 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine, Ru 24969, and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) failed to substitute completely. The 5-HT1/5-HT2 antagonists BC 105, metergoline, and methysergide completely blocked the MK 212 cue, while the selective 5-HT2 antagonists ketanserin and pirenperone, the dopamine antagonists haloperidol and spiperone, and the beta-noradrenergic antagonist propranolol were without effect. The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain. The complete antagonism by 5-HT1/5-HT2 but not by selective 5-HT2, antagonists suggests the possibility that 5-HT1 receptors mediate the stimulus properties of MK 212. Further research is needed to support this hypothesis and to investigate the relative role of 5-HT and other neurotransmitters in the stimulus effects of MK 212.

Animals↗
PubMed1986

Agonist and antagonist effects of prototype opiate drugs in fentanyl dose-dose discrimination.

The experiments characterized the effects of fentanyl, morphine, naloxone, cyclazocine, nalorphine, ketocyclazocine and N-allylnormetazocine in rats that were trained to discriminate 0.04 mg/kg from 0.02 mg/kg fentanyl (dose-dose discrimination). The data are compared to results obtained previously in rats discriminating 0.04 mg/kg fentanyl from saline (drug-saline discrimination). In the dose-dose discrimination fentanyl and morphine produced responding appropriate to 0.04 mg/kg fentanyl at doses which were 3.0- and 1.6-fold higher, respectively, than in drug-saline discrimination. Naloxone antagonized the stimulus effects of 0.04 mg/kg fentanyl at 9.8-fold lower doses than in drug-saline discrimination. The dose-effect curves of fentanyl and naloxone in rats discriminating 0.04 mg/kg from 0.02 mg/kg fentanyl, were steeper than in rats discriminating 0.04 mg/kg fentanyl from saline. While cyclazocine, nalorphine and N-allylnormetazocine acted as mixed and partial agonists/antagonists in drug-saline discrimination, those compounds acted as pure and complete antagonists of 0.04 mg/kg fentanyl in dose-dose discrimination. The rank order of compounds in antagonizing the stimulus effects of 0.04 mg/kg fentanyl in dose-dose discrimination was naloxone greater than N-allylnormetazocine greater than cyclazocine greater than nalorphine. It is suggested that a greater magnitude of opiate activity is required for producing generalization with the same 0.04 mg/kg dose of fentanyl in dose-dose as compared with drug-saline discrimination. Dose-dose discrimination may afford a more accurate method of the discriminative stimulus properties of drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Substitution and cross-tolerance profiles of anorectic drugs in rats trained to detect the discriminative stimulus properties of cocaine.

Rats were trained to discriminate cocaine, 10.0 mg/kg, using a two-lever operant procedure. Dose-effect data were determined for the substitution of cocaine, diethylpropion, methylphenidate, phenmetrazine, phentermine, and fenfluramine for the cocaine stimulus. All of these drugs, except fenfluramine, substituted fully for the cocaine stimulus. Subsequently, training was halted and cocaine, 20 mg/kg/8 h, was administered for 9 days, and dose-effect data were redetermined for all of these drugs on days 7-9 of chronic administration. Chronic administration of cocaine produced tolerance to the stimulus properties of cocaine, and cross-tolerance to the stimulus properties of methylphenidate, phenmetrazine, and phentermine, such that doses approximately two-fold higher than those used acutely were necessary to reproduce the original effect; the potency for the substitution of diethylpropion for the cocaine stimulus was decreased greater than four-fold; and fenfluramine still failed to substitute for the cocaine stimulus. These data suggest that 1) a common mechanism may mediate tolerance to the discriminative stimulus properties of cocaine, methylphenidate, phenmetrazine, and phentermine, and 2) tolerance in the drug discrimination procedure may have potential for establishing a comprehensive evaluation of dependence liability of CNS stimulants.

Animals↗
PubMed1988

Blockade of the discriminative stimulus effects of cocaine in rhesus monkeys with the D1 dopamine antagonist SCH 23390.

To investigate the role of D1 dopamine receptors in the discriminative stimulus effects of cocaine, two rhesus monkeys were trained in a two-lever, food-reinforced, drug discrimination paradigm to discriminate cocaine (0.2 mg/kg, IM) from saline. Administration of various doses of cocaine resulted in a dose-related increase in the percentage of responses that occurred on the drug-appropriate lever. Administration of the D1 antagonist SCH 23390 20 min before cocaine reduced drug-appropriate responding from 100% to 0% in all subjects and increased by 4-8-fold the cocaine dose necessary to induce drug-appropriate responding. A mutual antagonism of the rate-decreasing effects of cocaine and SCH 23390 was also observed. These findings suggest that D1 receptors play a significant role in the discriminative stimulus and rate-decreasing effects of cocaine.

Animals↗
PubMed1987

Phencyclidine (PCP)-like discriminative stimulus effects of metaphit and of 2-amino-5-phosphonovalerate in pigeons: generality across different training doses of PCP.

Pigeons were trained to discriminate either a fixed dose of PCP (1 mg/kg; n = 3) or a progressively decreasing dose (1-0.56-0.32 mg/kg; n = 4) from saline. Lowering of the training dose shifted the dose-effect curve for PCP's discriminative stimulus effects about 5-fold to the left, in a parallel manner, but did not decrease the accuracy of the discrimination performance and did not significantly increase the extent to which pentobarbital and chlordiazepoxide produced PCP-appropriate responding. Dose-effect curves based on binary generalization data were evaluated statistically with new methods that may be more appropriate than those used previously. Metaphit, a proposed PCP-receptor acylator, and 2-amino-5-phosphonovalerate (AP5), an N-methyl-D-aspartate (NMDA) antagonist, produced complete PCP-appropriate responding in the high training dose group only at doses that suppressed the rate of responding and that produced ataxia. However, 4-fold lower doses of metaphit and AP5, which did not produce directly observable behavioral effects, were found to substitute completely for PCP in the low training dose group. These data support the notion that PCP, metaphit, and AP5 have a common discriminative effect in pigeons.

2-Amino-5-phosphonovalerate↗
PubMed1987

Effects of pyrazolopyridines and a triazolopyridazine on the pentobarbital discriminative stimulus.

Rats were trained to discriminate injections of racemic pentobarbital (5.0 mg/kg) from saline in a two-lever drug discrimination task. After stable discrimination performance was attained, stimulus generalization studies were conducted with another barbiturate (barbital), benzodiazepine derivatives (diazepam and chlordiazepoxide), pyrazolopyridine derivatives (etazolate, cartazolate, and tracazolate), and a triazolopyridazine (CL 218, 872). The pentobarbital stimulus generalized to all of these compounds, except cartazolate. In addition, the administration of the benzodiazepine receptor antagonist flumazepil prior to benzodiazepine or triazolopyridazine administration produced a dose-related antagonism of each generalization. In contrast, the administration of flumazepil before barbiturate or pyrazolopyridine (i.e., etazolate or tracazolate) injection resulted in no attenuation of these generalizations. The results indicate that while certain barbiturates, benzodiazepines, pyrazolopyridines and triazolopyridazines are capable of producing similar stimulus effects, the behavioral actions of these agents can be differentiated on the basis of their susceptibility to antagonism by flumazepil.

Animals↗
PubMed1993

Acoustic intensity discrimination by the cichlid fish Astronotus ocellatus (Cuvier).

The acoustic intensity discrimination ability of the oscar (Astronotus ocellatus), a cichlid fish, was investigated using an automated positive reward method. Intensity discrimination thresholds (delta I, in dB) for 7-s continuous pure tone signals were measured both as functions of sound intensity above thresholds, i.e., sensation levels, (SL)(+10 dB, +20 dB and +30 dB) and frequency (200 Hz, 500 Hz, and 800 Hz). delta I at 500 Hz for +10 dB, +20 dB, and +30 dB SLs are 8.9, 5.5, and 3.3 dB, respectively. delta I (at +20 dB SL) for 200 Hz, 500 Hz, and 800 Hz are 4.5, 5.5, and 9.3 dB, respectively. Despite having poor auditory sensitivity (narrow frequency range and high thresholds), the intensity discrimination ability of the oscar follows the general trends of previously studied fish species, however, with higher thresholds.

Acoustic Stimulation↗
PubMed1987

Amphetamine impairs the discriminative performance of rats with dorsal noradrenergic bundle lesions on a 5-choice serial reaction time task: new evidence for central dopaminergic-noradrenergic interactions.

A series of experiments examined the effects of lesions of the dorsal noradrenergic bundle (DNAB), induced by 6-hydroxydopamine (6-OHDA), on the behavioural response to systemic and intra-accumbens amphetamine, using a rat analogue of Leonard's 5-choice serial reaction time task for humans. Although the 6-OHDA DNAB lesion produced a profound depletion of cortical noradrenaline (NA) (to around 5% of control levels) it did not impair any aspect of performance on this task. Both systemic and intra-accumbens amphetamine increased behavioural measures of impulsivity of responding, but neither impaired discriminative accuracy in the sham-operated control rats. However, the DNAB lesioned rats did show a discriminative impairment following both low doses of systemic amphetamine, and intra-accumbens amphetamine. The latter effect was antagonised by systemic administration of the specific dopaminergic (DA) antagonist alpha-flupenthixol. The DNAB lesion did not alter the effect of amphetamine on any other behavioural measure, including speed and impulsivity of responding. These results suggest that although DA and NA participate in qualitatively different behavioural processes, the effects of DNAB lesions on attentional processes depend on the level of DA activity within the nucleus accumbens.

Amphetamine↗
PubMed1988

Discriminative stimulus effects of caffeine and benzphetamine in amphetamine-trained volunteers.

The discriminative stimulus (DS) and subjective effects of caffeine (100 and 300 mg, PO) and benzphetamine (12.5 and 50 mg, PO) were studied in 18 normal human volunteers trained to discriminate between d-amphetamine (10 mg) and placebo. d-Amphetamine increased ratings of drug liking and activity level and produced a profile of subjective effects characteristic of amphetamine and related psychomotor stimulants. The DS effects of d-amphetamine generalized only partially to caffeine and benzphetamine; mean percent d-amphetamine-appropriate responding was 42 and 58 after 100 and 300 mg caffeine, respectively, and 17 and 56 after 12.5 and 50 mg benzphetamine, respectively. Neither dose of caffeine affected ratings of drug liking or activity level, but 300 mg caffeine did produce a profile of subjective effects that partially overlapped with that produced by d-amphetamine. Benzphetamine 50 mg, but not 12.5 mg, increased ratings of drug liking and activity level and produced a profile of subjective effects qualitatively similar to, but weaker than, that produced by d-amphetamine. For both caffeine and benzphetamine, a close relationship was observed between their subjective effects and their ability to substitute for the DS effects of d-amphetamine. These results correspond well with findings obtained from similar studies conducted with laboratory animals, providing further support for the reliability and validity of human drug discrimination paradigms.

Adult↗
PubMed1988

Discriminative properties of phencyclidine in mice: generalization to ketamine and monohydroxy metabolites.

The discriminative properties of phencyclidine (PCP) and their generalization to the effects of ketamine and monohydroxylated PCP metabolites were examined in C57BL/6cr mice utilizing two-lever operant procedures. As previously reported for pigeons and rats, PCP was discriminable in this species at a training dose of 3.0 mg/kg. PCP discriminability generalized to test doses of the drug that did not influence response rates (as low as 1.75 mg/kg) and also to ketamine (10 mg/kg). Both PCP monohydroxylated metabolites were active in mice. PCP partially generalized to the monohydroxylated metabolite, 1-(1-phenylcyclohexyl)4-hydroxy piperidine (PCHP) but not to 1-(1-phenyl-4-hydroxycyclohexyl) piperidine (PPC), which is consistent with previous reports on rats. The generalization of the PCP stimulus to PCHP was not as extensive in mice as previously reported for rats, suggesting that it may be less potent in this species. Although PCP discriminability generalized to PCHP, this generalization required PCHP doses that would produce tissue concentrations much higher than could result from discriminable doses of PCP. Therefore, the PCHP metabolite does not appear to mediate PCP discriminability in C57BL/6cr mice.

Animals↗