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Biomedical subjects

H Anisman

Publications and source records attributed to H Anisman.

At least 163 records · Page 9Linked to original sources

Effects of dopamine receptor blockade on alimentary behaviors: home cage food consumption, magazine training, operant acquisition, and performance.

Administration of the dopamine receptor blocker pimozide (1.0 mg/kg) disrupted the initiation, but not the maintenance, of home cage food consumption. Likewise, the number of pellets consumed during magazine training was decreased among pimozide-treated rats during the first, but not the second day of training. The acquisition of a bar-press response for food reinforcement (using a retractable bar) was severely retarded by pimozide. However, such an impairment was not evident if animals initially received 2 training days in the absence of the drug. Further, among rats trained to bar press to asymptote using a nonretractable bar, pimozide reduced the within and between days bar-press rate such that performance was indistinguishable from that of animals placed on extinction in the absence of the drug treatment. When transferred from the pimozide treatment to extinction in the absence of drug, the response rate increased to the level observed during the first session of either extinction or pimozide in the continuous reinforcement condition. The results are discussed in terms of sensory-motor and reinforcement consequences of dopamine receptor blockade.

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Escape performance after inescapable shock in selectively bred lines of mice: response maintenance and catecholamine activity.

The effects of inescapable shock on subsequent escape performance and shock-elicited activity were examined in six lines of mice selectively bred for differences in general locomotor activity. The line differences in locomotor activity were found to be unrelated to the differences observed on shock-elicited activity. However, escape performance following exposure to inescapable shock was predictable from the levels of shock-elicited activity. Those lines that displayed the greatest decline in motor activity during shock likewise displayed the most pronounced escape deficits. The line differences in escape performance induced by inescapable shock could be mimicked by treatment with a tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine. As predicted, the lines that displayed the least interference after tyrosine hydroxylase inhibition exhibited the smallest reduction in levels of catecholamines. The effects on escape performance following inescapable shock are interpreted in terms of the role of response maintenance deficits produced by catecholamine depletion.

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Catecholamine depletion in mice upon reexposure to stress: mediation of the escape deficits produced by inescapable shock.

Immediately following exposure to 60 inescapable shocks, Swiss-Webster mice had significantly reduced hypothalamic norepinephrine (NE). Within 24 hr NE levels returned to control values. Reexposure to as few as 10 shocks 24 hr after initial stress exposure resulted in a significant decline of hypothalamic NE. Moreover, at this interval after inescapable shock, escape performance was severely disrupted, with a large proportion of mice exhibiting numerous failures to escape shock. Increasing brain dopamine (DA) and NE by L-dopa treatment prior to inescapable shock prevented the escape deficits. Conversely, pairing five inescapable shocks with NE depletion by FLA-63, or both DA and NE depletion by alpha-methyl-p-tyrosine, disrupted escape performance 24 hr later. Residual drug effects, state dependence, or sustained amine turnover could not account for the behavioral changes observed. Data are discussed in terms of catecholamine mediation of escape performance through variations in response maintenance abilities. Furthermore, it is suggested that the long-term effects of inescapable shock may be due to sensitization effects or conditioned amine depletion.

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Involvement of norepinephrine in startle arousal after acute and chronic d-amphetamine administration.

Treatment with d-amphetamine produced a dose-dependent increase in startle amplitude in response to a buzzer. This increase appeared to be a reflection of a sensitization effect, i.e., enhanced responsivity as a function of repeated stimulus presentations. Treatment with alpha-methyl-p-tyrosine, which reduced whole brain concentrations of dopamine (DA) and norepinephrine (NE), or treatment with FLA-63, which reduced only NE, antagonized the effects of d-amphetamine on the startle reflex, suggesting a role of NE in this behavior. Startle amplitude was also reduced following chronic d-amphetamine treatment. The effect of d-amphetamine on startle was found to be independent of changes in drug-induced locomotor excitation. The data of the present investigation, together with earlier reports, suggests that tolerance occurs to those behaviors that involve a noradrenergic component.

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Abatement of stimulus perseveration following repeated d-amphetamine treatment: absence of behaviorally augmented tolerance.

Acute administration of d-amphetamine results in animals perseverating between two compartments when placed in a free running Y-maze exploratory situation. Experiment 1 indicated that perseverative behavior was attenuated by making the arms of the maze distinctively different. Experiments 2 and 3 demonstrated that repeated amphetamine treatment reduced arms of the maze distinctively different. Exeriment 2 and 3 demonstrated that repeated amphetamine treatment reduced stimulus perseveration. Drug-induced locomotor activity and stereotypy were not affected by chronic drug administration. The course of the tolerance effect was not altered by pairing the repeated drug experience with Y-maze exposure. It was concluded that although stimulus factors are involved in the perseverative response, conditioning factors are not of primary relevance in determining the tolerance. It was also suggested that the mechanisms which subserve stimulus perseveration are different from those which mediate locomotor activity and stereotypy.

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Perseveration and rotational behavior elicited by d-amphetamine in a Y-maze exploratory task: differential effects of intraperitoneal and unilateral intraventricular administration.

Mice received either intraperitoneal (1.0, 3.0, 5.0, or 15.0 mg/kg) or unilateral intraventricular injection (50.0, 100.0 or 200.0 microgram) of d-amphetamine. Both routes of injection produced circling behavior in a dose-related fashion when animals were tested in a circular alley-way. In contrast, performance in a free running Y-maze alternation task was differentially affected by the route of administration. Whereas intraperitoneal injection induced perseveration (i.e., animals consecutively visited only two arms of the maze), intraventricular injection augmented alternation behavior normally seen in saline-treated mice. It was suggested that Y-maze performance following intraventricular d-amphetamine injection reflects response perseveration, whereas systemic d-amphetamine treatment produced stimulus perseveration (repetition of location rather than direction). Moreover d-amphetamine-induced circling produced by intraperitoneal administration probably is an artifact of drug-induced stimulus perseveration as opposed to motor biases observed following intraventricular injections.

Animals↗

Simple and compact cannula system for mice.

A small and simple device is described for applying substances to the brain of freely moving mice. The effectiveness of the technique was evaluated by intraventricular injections of d-amphetamine sulfate. It was observed that intraventricular injections of d-amphetamine (50-200 microgram) produced a dose dependent increase in activity.

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Interaction between cholinergic and catecholaminergic agents in a spontaneous alternation task.

Spontaneous alternation was examined in a free running Y-maze task after various pharmacological manipulations. Whereas scopolamine reduced alternation to chance levels, d-amphetamine in some doses resulted in alternation significantly below chance (perservation). Physostigmine treatment increased levels of alternation whereas reserpine was without effect. Concurrent administration of drugs revealed that reserpine effectively reversed the effects of scopolamine, while the perseveration induced by d-amphetamine was antagonized by physostigmine. When animals were pre-exposed to the Y-maze the effects of d-amphetamine were enhanced, but effects of scopolamine were not modified. Finally, scopolamine treatment augmented the perseverative effects of d-amphetamine. It was suggested that cholinergic agents modify alternation by effects on habituation. On the other hand d-amphetamine produces genuine perseveration without effects on habituation per se. Alternation performance and perseveration were suggested to be mediated by the interaction between the distinct behavioral effects of cholinergic and catecholaminergic activity.

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Effects of scopolamine and d-amphetamine on locomotor activity before and after shock: a diallel analysis in mice.

The effect of shock on locomotor activity was evaluated in three strains of mice (A, DBA/2 and C57BL/6) after treatment with scopolamine (1.0 mg/kg) and d-amphetamine (10.0 mg/kh). The effectiveness of either drug in incrasing locomotor activity was strain dependent. Both drugs eliminated behavioral suppression induced by shock, and in A and DBA/2 mice shock augmented the locomotor stimulation induced by d-amphetamine. In another experiment the behavior of the 6 F1 hybrids was examined in relation to the parent strains. It was observed that locomotor activity in the F1's could resemble that seen in one parent in the saline condition, but the other parent after treatment with d-amphetamine. Similarly, the F1 behavior in the amphetamine condition was not predictive of the behavior seen after shock plus amphetamine. The results suggest that general activity, locomotor activity after amphetamine treatment, and responsiveness following shock in amphetamine-treated mice are mediated by different genetic mechanisms.

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Genetic and ontogenetic variations in locomotor activity following treatment with scopolamine or d-amphetamine.

Highly inbred mice of 3 strains (A/J, DBA/2J, and C57BL/6J) were tested in an open field at 14, 21, or 28 days of age. Ten minutes prior to testing, mice received treatment of saline, scopolamine (.5 or 1.0 mg/kg of body weight), or d-amphetamine (.5, 1.0, or 5.0 mg/kg). The d-amphetamine (5.0 mg/kg) increased activity in all strains at 14 days and 28 days of age, and at 21 days significantly increased activity in all except the C5BL/6. In contrast, increased activity with the scopolamine treatment was seen in DBA/2 at 21 days, but not in A and C57BL/6 until 28 days postnatally. The data support a caudal-rostral gradient of brain development with the inhibitory cholinergic system developing more slowly than the excitatory catecholamine system. In addition, strain-specific differences in activity levels are discussed in relation to the differential rates of chloinergic maturation.

Age Factors↗

Dissociation of the effects of scopolamine and d-amphetamine on a spontaneous alternation task.

The immediate and carry-over effects of scopolamine and d-amphetamine were evaluated in a free running Y-maze spontaneous alternation task. The immediate effect of scopolamine (1.0 mg/kg) or d-amphetamine (5.0 mg/kg) was to reduce alternation to chance or to levels significantly below chance (perseveration), respectively. On a second, non-drug test day alteration decreased in saline treated animals, but increased among mice which received scopolamine on Day 1. In contrast, upon retesting in the non-drug state, the performance of animals initially treated with d-amphetamine resembled that of saline treated mice. Subsequent experiments revealed that these effects could not be attributed to drug effects on peripheral mechanisms, consolidation, residual drug action or drug dissociated learning. It was concluded that the behavioral effects of scopolamine and d-amphetamine are qualitatively different. Whereas scopolamine disrupts habituation, d-amphetamine induces perseveration independently of any effects on habituation.

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Role of stimulus locale on strain differences in active avoidance after scopolamine of D-amphetamine treatment.

Three strains of mice were trained in a shuttle avoidance task following treatment with scopolamine (2.0 mg/kg) or d-amphetamine (3.0 mg/kg). When required to run towards light (CS) to avoid shock, A/J mice acquired the response more readily than DBA/2J or C57BL/6J mice. However, when required to run away from the light, the strain differences were eliminated. Under both testing conditions scopolamine and d-amphetamine augmented the performance of A/J mice, but had no effect of even disrupted performance of C57BL/6J. In DBA/2J mice d-amphetamine augmented performance only in the toward condition. Results were interpreted to support the hypothesis that scopolamine and d-amphetamine improve performance by response-disinhibition and response excitation, respectively. The presence of associative difficulties limit the effects of these agents.

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