In male Sprague Dawley rats, the first experience with a 2.5 mg/kg, ip, dose of amphetamine will induce an increase in locomotor activity in a large majority of the subjects compared to the untreated controls (see Fig. 2).
Motor Activity and Stereotypy. Fig. 1. Effect of d-amphetamine sulfate on locomotor activity in two separate groups (n=8) of male Sprague Dawley rats. The amphetamine was injected intraperitoneally a few seconds before the rats were individually placed in a dark force-plate actometer for a 1-h recording session. Data are based on the rats' first exposures to the apparatus. The saline group exhibited habituation during the first 40 min, and distance traveled remained low for the remainder of the hour. Compared to the saline group, the amphetamine-treated rats showed hyperactivity throughout the hour. Over the entire hour the saline group mean distance traveled was 59.71 m (s.e.m. 7.23 m), and the amphetamine-treated group traveled 133.51 m (s.e.m. 6.59 m).
However, when given repeatedly, the same dose of amphetamine predominantly evokes, a syndrome characterized by an absence of locomotion accompanied by rapid head movements that have been described as "sniffing" and/or "head bobbing". This syndrome is focused stereotypy or the "stationary phase'' of the amphetamine response, and it has been observed in observation arenas as large as 3.0 m x 3.5 m (Schiorring 1971).
The focused stereotypy score in Fig. 2 was calculated by combining a quantitative measure of spatial confinement with the variance of vertical force variation within the boundaries of the space used (see Fowler et al. 2007a for details). This score is low for a sleeping animal (high spatial confinement but low force variance because of a lack of "in-place" movements). The focused stereotypy score is also low when spatial confinement is low (movements are dispersed across the floor), despite the presence of high force variance associated with ambulation. When spatial confinement is pronounced and force variance is also high, a high focused stereotypy score is obtained. In Fig. 2, the switch from first-dose locomotor stimulation to tenth-dose substantial focused stereotypy (Fig. 2, panel b) can be appreciated by comparing the distance traveled data of Injection 1 (panel a, triangles) with the same measure for Injection 10 (panel a, squares), during the second 30 min of the session. Correspondingly, during the same time period, the focused stereotypy scores after Injection 1 were near zero, but averaged higher than 1 after Injection 10. This change in response topography from locomotion to stationarity and focused stereotypy is the result of a ► sensitization process, whereby rats become more sensitive to amphetamine or other psycho-motor stimulants as repeated dosing ensues. After injection 10, distance traveled (see Fig. 2, panel a, squares) did not drop to no-drug levels because three rats did not make a complete switch to focused stereotypy and continued to display substantial locomotor activation. However, all but one of the eight rats after the tenth injection showed a decrease in distance traveled compared to Injection 1. The aberrant rat actually exhibited evidence of sensitization of locomotor response, as suggested by its 67.9% increase in distance traveled between injection 1 and 10. Two important points can be made from these observations: (1) Individual differences in response to drugs are to be expected, especially when genetically heterogenous outbred strains of rats are used, and (2) when amphetamine or similar drugs are under study, at doses near the threshold for expression of focused stereotypy, the observed behavioral effect may be in opposite directions, with a subset of rats showing increased locomotor activity and another subset exhibiting locomotor suppression.
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