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PubMed1987

Toward a universal law of generalization for psychological science.

A psychological space is established for any set of stimuli by determining metric distances between the stimuli such that the probability that a response learned to any stimulus will generalize to any other is an invariant monotonic function of the distance between them. To a good approximation, this probability of generalization (i) decays exponentially with this distance, and (ii) does so in accordance with one of two metrics, depending on the relation between the dimensions along which the stimuli vary. These empirical regularities are mathematically derivable from universal principles of natural kinds and probabilistic geometry that may, through evolutionary internalization, tend to govern the behaviors of all sentient organisms.

Behavior↗
PubMed1984

Appetitive conditioning in neonatal rats: conditioned ingestive responding to stimuli paired with oral infusions of milk.

Components of rat pups' ingestive responses to orally infused milk came to be elicited by a novel odor conditioned stimulus (cedar) that had been repeatedly paired with milk infusions (Experiment I). Pups responded specifically to one odor, and they did not generalize their conditioned responding to either another odor or an unscented airstream (Experiment II). Ingestive responses could also be conditioned to a vibrotactile CS paired with milk, although levels of conditioned responding were lower than were obtained with an odor CS (Experiment III). Pups' internal state determined the effectiveness of training, in that pups that were removed from their dam for 24 hr showed reliable conditioned responding, while nondeprived pups and dehydrated pups did not (Experiment IV). Finally, pups showed retention of conditioned responding for at least several days after training (Experiment V).

Animals↗
PubMed1985

Discriminative stimulus properties and brain distribution of phencyclidine in rats following administration by injection and smoke inhalation.

Four male Sprague-Dawley rats were trained to discriminate IP injections of 3.0 mg/kg phencyclidine (PCP) from saline under a 2-lever fixed-ratio 32 schedule of food presentation. After reliable discriminative control of lever choice was established, other doses of injected PCP were tested resulting in dose-dependent increases in PCP-lever selection and dose-dependent decreases in rates of responding. When doses of PCP were administered by exposure to smoke from cigarettes containing PCP, a dose-dependent increase in PCP-lever responding was also observed. delta 9-Tetrahydrocannabinol administered via smoke exposure, up to doses which markedly suppressed response rates, did not result in PCP-appropriate responding, demonstrating the specificity of the PCP stimulus by the inhalation route. Brain levels and distribution of 3H-PCP were determined in rats administered doses calculated to result in 50% generalization by the IP injection or smoke inhalation routes. By both routes of administration roughly equivalent brain levels were attained and the distribution was relatively even across the seven brain areas analyzed. These results demonstrate the validity of using the injection route of administration when studying PCP experimentally, in spite of the fact that PCP is abused primarily by smoking.

Animals↗
PubMed1990

Development of conditional and equivalence relations without differential consequences.

Two experiments were conducted to establish conditional stimulus relations without differential consequences and to test for the emergence of other relations. In Experiment 1, 3 adults responded to match-to-sample displays in which sample-comparison pairs were constant while the second comparison presented with each pair changed periodically across trials. No differential consequences followed any comparison selections. All subjects learned conditional relations between constant samples and comparisons, but results of tests for transitivity in those relations were equivocal. In Experiment 2, 4 children were given unreinforced training and testing similar to that provided to the adults in Experiment 1, with procedural refinements. One child learned conditional relations and demonstrated emergent relations that confirmed the development of two four-member equivalence classes. Another child learned the conditional relations but did not demonstrate any emergent relations reliably. A 3rd child, after reinforced training on two conditional relations, learned four new conditional relations without differential consequences and demonstrated symmetry but not equivalence in the trained relations. The 4th child did not learn the conditional relations. These findings emphasize the importance of careful construction of tests for stimulus equivalence and suggest a need for critical analyses of the apparent emergence of untrained stimulus relations on unreinforced tests that has been observed in several stimulus equivalence studies.

Adult↗
PubMed2003

Apparatus bias and place conditioning with ethanol in mice.

RATIONALE: Although the distinction between "biased" and "unbiased" is generally recognized as an important methodological issue in place conditioning, previous studies have not adequately addressed the distinction between a biased/unbiased apparatus and a biased/unbiased stimulus assignment procedure. Moreover, a review of the recent literature indicates that many reports (70% of 76 papers published in 2001) fail to provide adequate information about apparatus bias. This issue is important because the mechanisms underlying a drug's effect in the place-conditioning procedure may differ depending on whether the apparatus is biased or unbiased. OBJECTIVES: The present studies were designed to assess the impact of apparatus bias and stimulus assignment procedure on ethanol-induced place conditioning in mice (DBA/2 J). A secondary goal was to compare various dependent variables commonly used to index conditioned place preference. METHODS: Apparatus bias was manipulated by varying the combination of tactile (floor) cues available during preference tests. Experiment 1 used an unbiased apparatus in which the stimulus alternatives were equally preferred during a pre-test as indicated by the group average. Experiment 2 used a biased apparatus in which one of the stimuli was strongly preferred by most mice (mean % time on cue = 67%) during the pre-test. In both studies, the stimulus paired with drug (CS+) was assigned randomly (i.e., an "unbiased" stimulus assignment procedure). Experimental mice received four pairings of CS+ with ethanol (2 g/kg, i.p.) and four pairings of the alternative stimulus (CS-) with saline; control mice received saline on both types of trial. Each experiment concluded with a 60-min choice test. RESULTS: With the unbiased apparatus (experiment 1), significant place conditioning was obtained regardless of whether drug was paired with the subject's initially preferred or non-preferred stimulus. However, with the biased apparatus (experiment 2), place conditioning was apparent only when ethanol was paired with the initially non-preferred cue, and not when it was paired with the initially preferred cue. These conclusions held regardless of which dependent variable was used to index place conditioning, but only if the counterbalancing factor was included in statistical analyses. CONCLUSIONS: These studies indicate that apparatus bias plays a major role in determining whether biased assignment of an ethanol-paired stimulus affects ability to demonstrate conditioned place preference. Ethanol's ability to produce conditioned place preference in an unbiased apparatus, regardless of the direction of the initial cue bias, supports previous studies that interpret such findings as evidence of a primary rewarding drug effect. Moreover, these studies suggest that the asymmetrical outcome observed in the biased apparatus is most likely due to a measurement problem (e.g., ceiling effect) rather than to an interaction between the drug's effect and an unconditioned motivational response (e.g., "anxiety") to the initially non-preferred stimulus. More generally, these findings illustrate the importance of providing clear information on apparatus bias in all place-conditioning studies.

Animals↗
PubMed2001

Selective activation of accumbens neurons by cocaine-associated stimuli during a water/cocaine multiple schedule.

Electrophysiological recording procedures were used to examine the responsiveness of nucleus accumbens (Acb) neurons to stimuli associated with cocaine delivery during a multiple schedule for water reinforcement and cocaine self-administration. Rats (n=9) were trained to press one lever for water reinforcement (0.05 ml/resp.; fixed ratio 1; FR1; 15 min) and a second spatially distinct lever for intravenous cocaine (0.33 mg/infusion; FR1; 2 h). The delivery of each reinforcer was signaled by different auditory stimuli. Of 101 neurons, 52 cells were classified as phasically active, exhibiting one of four well-defined types of patterned discharges relative to the water- or cocaine-reinforced response [J. Neurosci., 14(12) (1994) 7735; J. Neurosci., 20(11) (2000) 4255]. Acb cells were examined in test sessions consisting of 'probe' trials during which the stimulus previously paired with cocaine infusion was randomly presented in a response-independent manner during the self-administration portion of the session. Results showed that only neurons that exhibited changes in firing rate within seconds following the reinforced response for cocaine (but not water) were activated by the stimulus. This finding indicates that the responsiveness of cocaine selective neurons to cocaine-associated stimuli likely represents a conditioned response as opposed to a generalized stimulus-evoked discharge.

Animals↗
PubMed1971

The removal and restoration of stimulus control.

When a well-learned circle versus ellipse discrimination was made impossibly difficult for the subjects (rhesus monkeys), the controlling stimulus-response topographies were replaced by competing topographies. The identification of two training conditions sufficient to reinstate the original discrimination permitted the following inferences: the original controlling topography had merely decreased in probability of occurrence, whereas the "strength" of the stimulus-response relation remained unchanged; discriminations along the apparently continuous circle-ellipse dimension actually involved several distinct stimulus-control topographies.

Animals↗
PubMed1998

Comparative characterisation of the discriminative stimulus properties of clozapine and other antipsychotics in rats.

The discriminative stimulus properties of the prototypical atypical neuroleptic clozapine (5 mg/kg, IP) were characterised in rats using a fixed ratio assay. Clozapine induced full dose-related generalization in the absence of response suppression. Amphetamine and pentylenetetrazol failed to generalise at doses known to be discriminable, showing a degree of specificity for the clozapine cue. The typical neuroleptics haloperidol and loxapine induced minimal (20%) generalization at doses with marked behavioural effects; thus clozapine discrimination dissociates clozapine from typical neuroleptics. Atypical neuroleptics which are not clozapine congeners produced weak partial generalization when tested up to the highest doses that could be studied. The maximal levels of generalization induced by these agents were: amisulpiride 28%, risperidone 40% and sertindole 50%. Clozapine congeners typically caused more generalization, the novel pyridobenzoxapine JL13 inducing 70% maximal generalization. Most generalization (83%) was seen with the clozapine congener seroquel, although in contrast to clozapine, it only generalised at doses with marked effects on responding, so that no drug mimicked clozapine fully. Surprisingly, the clozapine congener olanzapine only induced a maximal level of 38% generalization. This apparently anomalous finding is attributed to an inability to test high doses of the drug due to its rate-suppressant actions. The clozapine cue can be used to rank atypical neuroleptics in terms of their similarity to clozapine in vivo. The clozapine cue is probably a compound cue, since only agents showing "polyvalent" receptor pharmacology induced substantial generalization.

Animals↗
PubMed1986

Discriminative properties of the psychostimulant dl-cathinone in a two lever operant task. Lack of evidence for dopaminergic mediation.

In order to analyse further the discriminative stimulus properties of stimulant drugs, rats were trained to discriminate 2.0 mg/kg of dl-cathinone in a two-lever operant task. Dose-related generalization was seen to cathinone itself and to a wide range of stimulant drugs including d-amphetamine, cocaine, methylphenidate, pipradrol and cathine, i.e. (+)norpseudoephedrine. The high degree of specificity of the cathinone cue at the specific training dose studied was shown by the fact that the following nonstimulant drugs failed to generalize at all to cathinone, even in large doses--haloperidol, chlordiazepoxide, fenfluramine and fentanyl. The cathinone cue at 2.0 mg/kg was probably of central origin because phydroxyamphetamine (a polar congener of amphetamine) failed to generalize to cathinone at a dose nearly 50 times the ED50 for amphetamine generalization. Phenylethylamine (PEA; alpha-demethylamphetamine) and deuterated phenylethylamine (alpha, alpha, d2-PEA), a long acting derivative of phenylethylamine which is resistant to metabolism by monoamine oxidase, produced at most partial (60%) generalization to cathinone, even in large doses. alpha-Demethylcathinone failed to generalize at all to cathinone at doses up to 10 times the ED50 for cathinone. Thus, the alpha-methyl groups of both amphetamine and cathinone are important in determining their cue properties. The involvement of dopaminergic systems in the cathinone cue was investigated by examining generalization to apomorphine and antagonism by haloperidol. Apomorphine produced at most 29% generalization to cathinone. Haloperidol, at doses up to 0.3 mg/kg, produced at most 50% antagonism of both the cathinone cue and of the ability of amphetamine to substitute for cathinone. It is suggested that the evidence for dopaminergic mediation of the cue properties of cathinone and of other CNS stimulants is somewhat tenuous, whilst endogenous phenylethylamine may play some part in the mediation of the stimulant cue. Haloperidol, alone and in conjunction with amphetamine or cathinone, produced a remarkable tendency for subjects to emit a greater proportion of their total responses on the inoperative rather than the operative lever than was seen after saline or injections of vehicle. This action of a neuroleptic drug suggests, in accordance with Colpaert, Niemegeers and Janssen (1977), that in drug discrimination antagonism studies involving neuroleptics, and perhaps other drugs, quantal (lever selection) rather than quantitative (percentage of responses on the drug lever) indices may be the procedures of choice.

Alkaloids↗