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PubMed1985

The morphogenesis of stereotyped behavior induced by the dopamine receptor agonist apomorphine in the laboratory rat.

The seemingly unrelated stereotyped locomotor "acts" reported in the literature to be produced by apomorphine in rats are shown to be composites, whose form and sequence are determined by the particular values of a few component variables which form a common denominator in each of the behaviors. Three variables, continuous snout contact, forward progression and turning, account for much of the behavior. In the course of the drug's action these emerge in succession and vary in amount, the latter two successively reaching a peak and subsiding. The interaction between forward progression and turning yields in sequence, forward walking, circling, revolving, tight pivoting and finally side-to-side movements of the forequarters around the relatively stationary hindquarters. Later behaviors in this list are gradually incorporated into the sequence as earlier ones are eliminated. The course of change in forward progression and turning is also reflected in changes in the sequence and in the direction of stepping of each of the four legs. The order in which the behavior unfolds under the drug is opposite to that manifested in ontogeny and in recovery from lateral hypothalamic damage, suggesting that at the particular high dose used, apomorphine is acting not only to activate the behavior but also to shut it down.

Animals↗
PubMed1987

Long-lasting effects of escalating doses of d-amphetamine on brain monoamines, amphetamine-induced stereotyped behavior and spontaneous nocturnal locomotion.

The repeated intermittent administration of relatively low doses of amphetamine (AMPH) produces an enduring hypersensitivity to the motor stimulant effects of AMPH (behavioral sensitization), and this is accompanied by enhanced mesotelencephalic dopamine (DA) utilization/release. In contrast, chronic treatment with very high doses of AMPH does not produce sensitization, but is neurotoxic, resulting in the depletion of brain DA (and often other monoamines). However, gradually escalating doses of AMPH provide protection against the neurotoxic effects of higher doses given later. Therefore, the purpose of the present experiment was to determine if a regimen of gradually escalating doses of AMPH, culminating in much higher doses than usually used to study sensitization, would produce neural and behavioral changes associated with AMPH neurotoxicity (DA depletion) or behavioral sensitization (increased DA utilization). Female rats were given 60 injections (2/day) of increasing (1 to 10 mg/kg) doses of d-AMPH, culminating in rats receiving 20 mg/kg/day for four consecutive days. This treatment did not deplete brain DA or serotonin, but did produce a long-lasting enhancement (at least 12 days) in striatal and nucleus accumbens DOPAC concentrations, and DOPAC/DA ratios. These neurochemical changes were accompanied by an enduring hypersensitivity to the stereotypy-producing effects of a subsequent AMPH 'challenge.' In contrast to this enhanced response to a challenge, AMPH-pretreated rats showed a marked reduction in spontaneous nocturnal motor activity. It is concluded that rats can be given escalating doses of AMPH, which mimic to some extent the AMPH 'runs' common in addicts and that this produces neural and behavioral changes consistent with the development of sensitization; not neurotoxicity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Methylphenidate in severely retarded residents and the clinical significance of stereotypic behavior.

An attempt was made to evaluate a model predicting stimulant drug response based on attentional characteristics of the participants. Twenty-eight severely and profoundly mentally retarded residents took part in a double blind, placebo controlled trial of methylphenidate (Ritalin). Methylphenidate was administered, for one week each, in a low dose of 0.3 mg/kg and a high dose of 0.6 mg/kg. The results failed to show any clinically relevant differences between placebo and active drug conditions with the exception that methylphenidate caused a significant reduction in food consumption. A variety of subject characteristics, including level of stereotypy, hyperactivity, and IQ were unrelated to drug effect. One positive finding, unrelated to drug effects, was that subdivision of the group by degree of stereotypy provided substantial clinical information about individual subjects.

Adolescent↗