Refining the critical period for methamphetamine-induced spatial deficits in the Morris water maze

Abstract

Rationale: Neonatal administration of methamphetamine (MA) to rats from postnatal day (P) 11 to 20, but not from P1 to P10, produces lasting deficits in spatial learning and memory. The preweaning period of development in the rat corresponds to human third trimester hippocampal development and because of the increased use of MA in women of childbearing age, there is a greater likelihood that fetuses will be exposed to this drug. Development of the hippocampus is dependent upon many factors, including an optimal level of corticosterone (CORT). We have demonstrated that the CORT response of animals on P11 to MA is protracted relative to administration on P15 or P20. Interestingly, the P11 animals are still in the stress hyporesponsive period. Objectives: We postulated that because of the prolonged CORT response on P11, the effects of MA on spatial learning and memory may be confined to a shorter period of exposure. Methods: Neonatal rats were administered MA (10 mg/kg) 4 times daily from either P11 to P15 or from P16 to P20, raised to adulthood and tested against animals only administered saline (SAL) from P11 to P20 for anxiety, swimming ability, and spatial learning and memory. Results: Animals exposed to MA, regardless of exposure period, tended to be less anxious in the Zero maze relative to SAL animals. No differences were noted for swimming ability. Only animals exposed to MA from P11 to P15 demonstrated deficits in spatial learning and memory during acquisition as well as during a shifted platform phase where learning a new position was required. Conclusions: The results demonstrate that spatial learning and memory deficits produced by MA administration are dependent upon when the exposure of the animal occurs and appears to be during the period of development in the rat when the response to threatening environments, stressors, is greatly reduced.

Progression of multiple behavioral deficits with various ages of onset in a murine model of Hurler syndrome

“…We examined animals at 2 months of age as described previously (Williams et al, 2003). The apparatus consists of a circular runway divided in 4 equal quadrants.…”

Alterations in Body Temperature, Corticosterone, and Behavior Following the Administration of 5-Methoxy-Diisopropyltryptamine (‘Foxy’) to Adult Rats: a New Drug of Abuse

“…The platform was first located in the SW quadrant for the acquisition phase, in the NE quadrant for the reversal phase, and in the NW quadrant for the shift phase. The start positions were defined previously (Williams et al, 2003a) and included only positions that did not release the animal in the goal quadrant. For example, when the platform was located in the SW quadrant, the starting points were N, E, NW, SE, and when the platform was located in the NE quadrant, the starting points were S, W, SE, and NW, and for the NW quadrant, starting points were S, E, SW, and NE.…”

Learning and memory after neonatal exposure to 3,4‐methylenedioxymethamphetamine (ecstasy) in rats: Interaction with exposure in adulthood

“…This test measures anxiety using an elevated zeroshaped apparatus (105 cm diameter and 10 cm path width) with two closed areas separating two open areas spaced evenly apart, as detailed previously (Williams et al, 2003a). The test was conducted under dim halogen lighting.…”

“…Straight channel-Straight channel swims, as described previously (Broening et al, 2001;Williams et al, 2003a), commenced 1 day after the elevated zero maze test. A trial was started with the rat facing the end wall of the channel at the opposite end from an escape ladder.…”

“…The animals were given 4 trials/day (2 min maximum/trial) separated by an intertrial interval of 15 s. For acquisition, the platform was located in the southwest quadrant, with north defined as the furthest position from the experimenter. The animal was started at distal positions (with head facing the wall) that did not include locations immediately adjacent to the platform quadrant, as defined previously (Williams et al, 2003a). These were NW, N, E, SE, but not W or S because the latter are close to the platform.…”