Adult Learning Deficits after Neonatal Exposure tod-Methamphetamine: Selective Effects on Spatial Navigation and Memory

Abstract

The effects of neonatal d-methamphetamine (MA) treatment on cued and spatial learning and memory were investigated. MA was administered to neonatal rats on postnatal days 11-20. All groups received four subcutaneous injections per day. Group MA40-4 received 40 mg. kg(-1). d(-1) of MA in four divided doses (10 mg/kg per injection). Group MA40-2 received 40 mg. kg(-1). d(-1) of MA in two divided (20 mg/kg/injection) and saline for the other two injections per day. Controls received saline for four injections per day. As adults, both MA groups showed no differences in swimming ability in a straight swimming channel. The MA40-4 group showed no differences in cued learning, but was impaired in hidden platform learning in the Morris water maze on acquisition. They also showed reduced memory performance on probe trials. Similar trends were seen on reversal learning and reversal probe trials. Reduced platform-size learning trials caused spatial learning impairments to re-emerge in the MA40-4 group. The MA40-2 group showed no differences in straight channel swimming, but was slower at finding the visible platform during cued learning. They were also impaired during acquisition and memory trials in the Morris hidden platform maze. They showed a similar trend on reversal learning and memory trials, but were not different during reduced platform-size learning trials. When the MA40-2 group's performance on hidden platform learning and memory trials was adjusted for cued trial performance, the spatial learning deficits remained. Deficits of spatial learning and memory are a selective effect of neonatal methamphetamine treatment irrespective of other learning and performance variables.

Developmental effects of ±3,4‐methylenedioxymethamphetamine on spatial versus path integration learning: Effects of dose distribution

“…Based to some extent on evidence that treatment with methamphetamine given on P11-20, using the same total daily amount of drug but divided and administered as two or four doses, produced different patterns of MWM double-reversal learning deficits (Vorhees et al, 2000), we sought to determine if this was a more general phenomenon. To test this, the present experiment compared three different dosing regimens of a different substituted amphetamine, MDMA.…”

“…This regimen increases the efficacy of the drug for reducing of brain monoamines while minimizing mortality (Sonsalla et al, 1989(Sonsalla et al, , 1991 compared to single or twice daily higher dose administrations. Developmentally, the same daily dose of methamphetamine given as four or two divided doses on P11-20 causes comparable effects on MWM acquisition and reversal learning, but four divided doses has larger effects on learning with a small platform, whereas the same total daily dose given as two divided doses has little effect on small platform learning (Vorhees et al, 2000). There are no data on the effects of dose distribution for developmental MDMA.…”

Morris water maze: procedures for assessing spatial and related forms of learning and memory

“…For example, if the starting platform is 10 × 10 cm, the reduced platform may be 5 × 5 cm. This reduction in platform size taxes the spatial accuracy requirements of the animal and has revealed the effects of some drugs or doses that are not seen during acquisition or reversal 16,20 . A reduced platform probe trial is also given 24 h after the end of this phase of testing.…”

“…Some of this stems from an under-appreciation for the aspects of the apparatus and testing procedures that are most salient for obtaining the best possible data. Here, we provide a description of the apparatus, its key features, and protocols that are effective and reliable for detecting drug/ lesion-induced changes in spatial learning and memory [16][17][18][19][20] or changes that arise as a result of genetic manipulations [21][22][23][24][25][26][27][28] . We also provide variations to the basic protocol that can be used to enhance assessment of spatial navigation and/or test for related types of learning (latent, discrimination, and cued learning or working memory).…”

Differential Effects of Amphetamines-Induced Neurotoxicity on Appetitive and Aversive Pavlovian Conditioning in Mice

“…In humans, METH-induced DA neurotoxicity is concurrent with impairments in recall memory (Chang et al, 2002;Simon et al, 2000;Thompson et al, 2004), and higher executive functions of the prefrontal cortex, such as decision-making (Rogers et al, 1999). In rats, exposure to moderate (Vorhees et al, 2000) and neurotoxic (Friedman et al, 1998) doses of METH disturbed spatial learning in the Morris water maze and the radial arm maze (Chapman et al, 2001). Similarly, extensive exposure to MDMA produces serotonergic neurotoxicity, that is, significant reduction of serotonin (5-hydroxytriptamine, 5-HT) and 5-HT transporters (5-HTT) in rats (Lyles and Cadet, 2003) and humans Semple et al, 1999).…”