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PubMed1979

Postnatal alpha-methylphenylalanine treatment effects on adult mouse locomotor activity and avoidance learning.

Neonatal mice were injected for five days with a combination of alpha-methylphenylalanine and phenylalanine to determine the influences of excess phenylalanine during development upon the behavior of these mice as adults. Spontaneous activity, bolus production, passive avoidance learning, simple active avoidance learning and complex active avoidance learning were tested in mice treated at two different postnatal periods. The results show that the treatments during development produced adult behavioral alterations compared to controls. The effects were most pronounced in mice treated in the postnatal period immediately after birth. The behavioral effects can be summarized as increased emotionality and generalized, stimulus-induced activity as well as decreased passive avoidance performance and complex active avoidance performance. These behavioral deficits are consistent with those usually reported in various models of human phenylketonuria.

Animals↗
PubMed1981

Caffeine discrimination in the rat.

Rats were trained to discriminate 32 mg/kg caffeine from saline in a two-lever appetitive task. Across a range of caffeine test doses (1-32 mg/kg) rats showed a dose related generalization to the training cue. At intermediate caffeine dose levels, caffeine appeared to produce a more potent cue on tests following saline-training days than after drug-training days. Several psychomotor stimulants (d-amphetamine, methylphenidate, nicotine and TRH) failed to generalize to the caffeine cue. In contrast, theophylline did generalize to caffeine at a dose roughly twice that of the caffeine training dose.

Animals↗
PubMed1982

Effects of apomorphine on appetitive conditioning in 6-hydroxydopamine treated rat pups.

Rat pups were treated on postnatal day 5 either with the combination of desmethylimipramine (DMI) and 6-hydroxydopamine (6-OHDA) to produce depletion of brain dopamine, or with control injections of saline. Two days later they were presented a novel anise odor paired with intraoral baby formula, and on the next day were tested for preference for the novel odor. Before conditioning and testing, animals were treated with either apomorphine (0.05 mg/kg) or isotonic saline. Performance of the conditioned appetitive response was impaired in dopamine depleted animals. In DMI/6-OHDA treated pups, apomorphine administration prior to conditioning produced an improvement in performance, but drug treatment prior to testing had no effect. In normal pups, apomorphine administration either before conditioning or testing produced impaired performance at testing.

Animals↗
PubMed1986

Relationship of plasma phencyclidine levels to phencyclidine discrimination in the pigeon.

Plasma phencyclidine levels were determined in pigeons trained to discriminate 1.5 mg/kg phencyclidine from saline under a second-order schedule using a color-tracking procedure. With both cumulative and non-cumulative dosing procedures, pigeons reliably discriminated plasma phencyclidine levels above 200 ng/ml. When the time course of phencyclidine discrimination was determined and compared with the time course of phencyclidine levels in plasma in a different group of birds, a similar relationship between discrimination and plasma phencyclidine was generally observed. Plasma phencyclidine levels did not correlate well with position responding observed in some birds after lower phencyclidine doses.

Animals↗
PubMed1986

Pharmacological changes induced by repeated exposure to phenylethylamine.

Mice receiving daily injections of phenylethylamine (PEA) exhibited an enhanced PEA-induced motor stimulation, beginning on day 21 of administration. The mice receiving PEA were also more sensitive to the stimulatory effect of amphetamine and PCP. There was no change in brain or hepatic monoamine oxidase activity nor in hepatic mixed function oxidase after this treatment, indicating that altered metabolism was not a factor in the sensitization. Striatal dopamine receptors, labelled by spiroperidol, were increased after the long-term PEA, suggesting that the sensitization may be due to increased dopaminergic receptor activity.

Animals↗
PubMed1989

Self-administration of phenylpropanolamine (PPA) by rats previously trained to self-administer amphetamine.

Central nervous system stimulation, similar to that observed for amphetamine, has been attributed to phenylpropanolamine (PPA). However, formal tests, using evaluation of locomotion or of self-administration, fail to reveal that PPA is a stimulant. Self-administration studies have trained rats to self-administer cocaine and then have attempted to switch rats to PPA with no success of transfer. The present study further examined the reinforcing properties of PPA (0.08, 0.16, and 0.32 mg/infusion, IV) in rats that were initially trained to self-administer d-amphetamine (0.005-0.08 mg/infusion) in a two-lever paradigm. Self-administration of amphetamine was a function of dose with 0.01 mg/infusion producing reliably high responding on the active lever. The proportion of active/inactive lever presses remained constant (0.60-0.80) across the amphetamine dose range. PPA was dose-dependently self-administered during the first hour of each session with rats responding at approximately 70% on the active lever. In contrast, responding on the active lever dropped off to approximately 48% when saline was substituted for amphetamine. These data document that rats with prior exposure to amphetamine will self-administer PPA during the initial portion of a three-hour test.

Amphetamine↗
PubMed1990

Partial cross-dependence on ethanol in mice dependent on chlordiazepoxide.

Mice which had been fed chronically a liquid diet containing chlordiazepoxide (CDP) showed spontaneous and Ro15-1788-induced withdrawal signs upon CDP withdrawal. Ethanol (1.5 g/kg) injected 5 min before Ro15-1788 injection almost completely suppressed the withdrawal signs induced by the benzodiazepine receptor antagonist. However, neither ethanol injection nor ethanol diet administration could prevent the loss of appetite and weight loss on day 1 of CDP withdrawal. Likewise, the addition of saccharin in the ethanol diets did not prevent the loss of appetite. Mice which had been fed the CDP diet followed by 9 days of ethanol treatment (CDP/ethanol) showed more severe hypothermia during ethanol withdrawal compared to mice which had been fed the control/ethanol diets. The CDP/ethanol mice also retained the increase in runway activity attained from the prior CDP treatment. The data indicate that CDP-dependent mice showed partial rather than full cross-dependence on ethanol.

Animals↗
PubMed1990

Multidimensional scaling of subjective judgements of drug similarities among ketocyclazocine, morphine, cyclazocine, naloxone and placebo.

Profiles of the subjective and physiologic effects of opioid drugs in man cannot be assigned with precision to specific opioid drug-receptor interactions. We administered a set of training doses of ketocyclazocine, morphine, cyclazocine, naloxone and placebo to 10 drug-using volunteers and obtained similarity judgements between each of 2 test doses of the drugs and a training dose. These data were submitted to multidimensional scaling analysis (INDSCAL) using both neighboring cells estimates and root mean square estimates to estimate missing cells in the data matrices. The results of these analyses are convergent, appear valid and indicate that there are three drug dimensions expressed in this data set: morphine versus placebo and naloxone; cyclazocine and ketocyclazocine versus placebo and naloxone; and ketocyclazocine versus cyclazocine. We interpret this result as supporting evidence that in the set of five drugs studied, three subjective states are induced.

Adult↗
PubMed1990

Drug discrimination in rats successively trained to discriminate diazepam and pentobarbital.

In Phase 1, rats were trained to discriminate either diazepam or pentobarbital from the no-drug condition. Diazepam, pentobarbital, triazolam, meprobamate, and zopiclone occasioned 100% drug-lever responding in tests under both training conditions; but the generalization gradients determined under the pentobarbital training condition were shifted to the right of those determined under the diazepam training condition. In Phase 2, the training drugs were reversed for the two groups, as well as which lever was paired with drug or no drug, in an effort to produce greater specificity of the Phase 2 discrimination. In Phase 2 tests, the Phase 1 training drug occasioned responding on the Phase 2 drug lever in all rats, suggesting that retraining overrode the Phase 1 discrimination. There were indications, however, that Phase 1 training influenced Phase 2 responding: 1) Rats ceased responding partway through no-drug training sessions using the former drug lever, and criterion performance was somewhat more difficult to maintain in Phase 2. 2) In Phase 2, dose-effect curves determined under pentobarbital training were shifted even further to the right of those determined under diazepam training than in Phase 1.

Animals↗
PubMed1993

Preliminary findings with the indirect 5-HT agonist dexfenfluramine on heroin discrimination and self-administration in rats.

In the present study, the effect of the 5-HT releaser/reuptake inhibitor dexfenfluramine in heroin self-administration and morphine (3 mg/kg) drug discrimination paradigms was examined. Dexfenfluramine (1 mg/kg) reduced heroin self-administration (heroin dose 0.03 mg/kg/infusion; FR5 schedule; 1-h session/day). This effect was antagonised by the 5-HT1/2 receptor antagonist metergoline (1 mg/kg). In the drug discrimination model, dexfenfluramine (0.5-2.5 mg/kg) produced no significant generalisation to a morphine cue, and also failed to modify the generalization curve to heroin. Dexfenfluramine (1 mg/kg) produced a slight decrement in response rate in the drug discrimination model and this effect was potentiated by heroin. The mechanism(s) by which dexfenfluramine reduces heroin self-administration remain to be determined, however substitution for heroin would seem unlikely. Furthermore, this effect of dexfenfluramine is probably mediated by either 5-HT1 or 5-HT2 receptors.

Animals↗
PubMed1981

Behavior analysis and experimental pharmacology.

This paper provides an introduction to the field of behavioral pharmacology. A brief description of the main characteristics of behavior analysis is followed by a review of the contributions of experimental pharmacology to behavior analysis and vice versa. Finally, a section on new procedures in behavioral pharmacology outlines experimental situations in which complex kinds of behavior can to studied. These include: (a) temporal discrimination; (b) preference to be free and informed; (c) commitment, choice and self-control; and (d) high-order concept formation.

Animals↗
PubMed1991

Increased generalization between drug-related interoceptive stimuli with delayed testing.

Although the flattening of generalization gradients over time has been widely investigated using exteroceptive stimuli, little attention has been given to generalization involving interoceptive stimuli. To investigate generalization between internal states, Sprague-Dawley rats were given either 0.835 ml/kg chloropent or 15 mg/kg sodium pentobarbital. Both drugs produced asymmetrical state-dependent retention of a passive avoidance response, that is, good retention in the "same state" conditions (i.e., the drug-drug and no drug-no drug conditions) as well as in the no drug-drug conditions but poor retention in the drug-no drug conditions, at both 1- and 7-day retention intervals. Furthermore, subjects trained in one drug state (pentobarbital or chloropent) demonstrated disrupted performance when tested 1 day later in another drug state, but good performance when tested 7 days later in the other drug state, indicating a decrement in the discriminability of the two drug states after 7 days. This outcome demonstrates that generalization gradients between drug states flatten over time. Moreover, these results suggest that memory for attributes of internal stimuli undergoes changes similar to those found for exteroceptive stimuli. Implications for contextual cues models of forgetting are considered.

Anesthetics↗
PubMed1983

Discrimination of monkey faces by split-brain monkeys.

Eighteen split-brain rhesus monkeys were tested with each hemisphere for the ability to learn to discriminate photographs of the faces of other monkeys. Seven subjects also ran tests of generalization to new photographs of the discriminated monkeys; these tests confirmed that facial features pertaining to individual monkeys were learned. Equal numbers of male and female monkeys and nearly equal numbers of right and left handed monkeys were tested. Over all the monkeys there was no significant advantage in learning with either the left or right hemisphere or with the hemisphere contralateral or ipsilateral to the preferred hand. The group of 9 female monkeys, however, did shown a significant advantage in learning with the left hemisphere. Furthermore, there was a tendency for monkeys older at the time of surgery to show greater hemispheric specialization.

Animals↗
PubMed1986

Hippocampal lesions disrupt classical conditioning of cross-modality reversal learning of the rabbit nictitating membrane response.

The role of the hippocampus and subiculum in classical conditioning of tone-light discrimination reversal learning of the rabbit nictitating membrane response was investigated using aspiration lesions of both limbic structures. Only two of seven animals with hippocampal-subicular damage successfully reached reversal criteria within 21 days of conditioning, although all hippocampectomized animals learned the initial discrimination at rates equivalent to those of two control groups. Thus, previously reported deficits in two-tone reversal learning seen after similar lesions are not due to increased within-modality generalization to the conditioned stimuli (CS) serving as the CS+ and CS-.

Animals↗
PubMed1990

Visual discrimination of discontinuous figures in the rabbit.

Rabbits were trained to discriminate between vertical and horizontal striations. After the 90% correct level had been reached transfer to vertical and horizontal rows of dots was studied. It was found that performance depended on the distance between adjacent dots. With angular dot separations (measured from the centers) larger than 4.9 degrees, performance was below the 75% correct level. This result is discussed in relation to the size of the receptive fields of orientation-selective neurons in the binocular visual cortex.

Animals↗
PubMed1990

Normal variation of P300 in children: age, memory span, and head size.

The P300 (P3) event-related brain potential was elicited in a group of 50 children and young adults (4-20 years). A simple auditory task was employed in which subjects indicated with a finger movement when a randomly occurring target tone (high pitch) was presented in a series of standard (low pitch) tones. The probability of the target tone was varied across conditions at 10%, 30%, or 50% to assess possible developmental changes in P300 amplitude. Memory capacity was assessed with forward and reverse digit spans. Circumference of the head also was measured. P300 latency decreased with age, and P300 amplitude tended to become larger with age. Polynomial regression analyses revealed significant quadratic trends in these relationships, with changes leveling off for older subjects. Digit span and head circumference also were related curvilinearly to P300 values. Multiple regression analysis indicated that changes in age and memory span both predicted significant changes in P300 latency and amplitude. Target stimulus probability generally affected all subjects in a similar fashion, although the strength of the correlational relationships tended to decline with increases in probability. Developmental changes for the N1, P2, and N2 components from the standard stimuli also were obtained. The results are discussed in terms of previous P3 findings for children and their implications for future studies.

Acoustic Stimulation↗
PubMed1989

Computer-assisted predictive mathematical relationship among electroshock voltage and duration and occurrence of convulsion in mice.

A microcomputer program in BASIC for predicting percentage of occurrence of electroshock-induced convulsion in mice was designed. A formula published by the author to express the mathematical relationship among the drug dose, the time, and the biological response was used in this program. Analysis of the actual, and the computer-assisted predicted percentages of occurrence of convulsion has shown that the program is fairly accurate in expressing convulsion response of mice as a function of the voltage and the duration.

Animals↗
PubMed1991

The effect of endotoxin and turpentine administration on intestinal permeability in the rat.

Intestinal permeability in 4-week-old rats has been assessed by the dual sugar (lactulose/mannitol) permeability test before and for two days after induction of systemic inflammation by various endotoxins and turpentine. Evidence of an inflammatory response to these agents was provided by marked reductions in food consumption and growth rate, hypoalbuminaemia, and a large increase in the plasma concentration of the acute-phase protein alpha-2-macroglobin. Abnormal values for intestinal permeability occurred only in animals which had been injected with E. coli 0111:B4 endotoxin. Neither turpentine nor the other endotoxins produced any detectable effect. Within 2-7h of the first exposure to a low dose, (3mg/kg) of either phenol or trichloroacetic extracts of E. coli 0111:B4 endotoxin, the lactulose:mannitol (L M ) ratio was elevated by 32% and 50% respectively (p < 0.05), but the rise was not sustained despite continued twice-daily injections of endotoxin. Administration of a higher dose, (10 mg/kg twice daily, phenol extract) resulted in diarrhoea, and a greater more persistent increase in the L M ratio; 115% (p < 0.05) 2-7h after the first injection, and 49% above control values, (p < 0.01) 24h later. The increase in L M ratio appeared to be due to a decrease in mannitol excretion. Total urinary lactulose also tended to fall, especially in rats given the high dose of endotoxin. It is concluded that a systemic inflammatory response does not necessarily lead to a change in intestinal permeability as measured by the dual sugar permeability test. The transient permeability changes observed following E. coli 0111:B4 administration may be a specific reaction to this material rather than to a more general systemic stimulus.

Journal Article↗