Dose-dependent changes in the locomotor responses to methamphetamine in BALB/c mice: Low doses induce hypolocomotion

Abstract

The overall goal of the present study was to determine the effects of different doses of (+)-methamphetamine (meth) on locomotor activity of Balb/C mice. Four experiments were designed to test a wide range of meth doses in BALB/c female mice. In Experiment 1, we examined locomotor activity induced by an acute administration of low doses of meth (0.01 and 0.03 mg/kg) in a 90-min session. Experiment 2 was conducted to test higher meth doses (0.3 – 10 mg/kg). In Experiment 3, separate sets of mice were pre-treated with various meth doses once or twice (one injection/week) prior to a locomotor challenge with a low meth dose. Finally, in Experiment 4, we tested whether locomotor activation would be affected by pretreatment with a low or moderate dose of meth one month prior to the low meth dose challenge. Results show that low doses of meth induce hypolocomotion whereas moderate to high doses induce hyperlocomotion. Prior exposure to either one moderate or high dose of meth or to two, low doses of meth attenuated the hypolocomotor effect of a low meth dose one week later. This effect was also attenuated in mice tested one month after administration of a moderate meth dose. These results show that low and high doses of meth can have opposing effects on locomotor activity. Further, prior exposure to the drug leads to tolerance, rather than sensitization, of the hypolocomotor response to low meth doses.

A vaccine against methamphetamine attenuates its behavioral effects in mice

“…In the first functional test, we demonstrate that the SMA-KLH vaccine alters the acute effects of MA in a dose-dependent manner. At low doses, MA can cause hypolocomotion (Kitahama and Valatx, 1979), a phenomenon we have confirmed and extended previously (Singh et al, submitted) as well as in the present paper. However, the duration of this prolonged hypolocomotor effect is shortened by the SMA-KLH vaccine (Fig.…”

“…MA and other psychostimulants, such as cocaine, increase locomotor activity at moderate doses and can induce stereotypic responses, such as sniffing, head bobbing, and other in-place activities, at higher doses (Antoniou et al, 1998; Brien et al, 1978; Ellinwood and Balster, 1974; Kuczenski and Segal, 1989). However, at very low doses, cocaine and amphetamine can cause hypolocomotion in rats and mice (George, 1989, 1990) and we recently confirmed this observation with MA in mice (Kitahama and Valatx, 1979; Singh et al, submitted). CPP is a procedure that has been used to assess the rewarding properties of many drugs (Bardo and Bevins, 2000; Carr et al, 1989; Schechter and Calcagnetti, 1993; Tzschentke, 1998).…”

A Markerless 3D Computerized Motion Capture System Incorporating a Skeleton Model for Monkeys

“…These findings are inconsistent with rodent studies in which acute MAP administration usually increased locomotor activity [36–38]. However, a previous monkey study reported that the effects of acute MAP administration on motor excitation were not consistent across species [29], which is consistent with the present study.…”

Sex differences in the acute locomotor response to methamphetamine in BALB/c mice

“…After the baseline period, mice were given a subcutaneous injection of either a low dose (1 mg/kg; Female: n=5, Male n=9) or high dose (4mg/kg; Female: n=5, Male n=5) of METH [(+)-methamphetamine hydrochloride, Sigma-Aldrich; St. Louis, MO, USA] dissolved in sterile PBS. These doses were chosen based on our previous work assessing METH-induced locomotor activity in female BALB/c mice [22]. After the injection, mice were placed back into the testing chamber and locomotor activity was recorded for an additional 90 min.…”

“…This divergent finding may be explained, in part, by their use of CD-1 mice, which were administered a high dose of METH (40 mg/kg) [15]. High doses of METH reliably induce hypolocomotion [22] and stereotypy [25], which would likely mask any potential sex differences in locomotor activity.…”