Effects of neonatal (+)‐methamphetamine on path integration and spatial learning in rats: effects of dose and rearing conditions

Abstract

Postnatal day (P)11-20 (+)-methamphetamine (MA) treatment impairs spatial learning and reference memory in the Morris water maze, but has marginal effects on path integration learning in a labyrinthine maze. A subsequent experiment showed that MA treatment on P11-15, but not P16-20, is sufficient to induce Morris maze deficits. Here we tested the effects of P11-15 MA treatment under two different rearing conditions on Morris maze performance and path integration learning in the Cincinnati water maze in which distal cues were unavailable by using infrared illumination. Littermates were treated with 0, 10, 15, 20, or 25 mg/kg x 4 per day (2 h intervals). Half the litters were reared under standard housing conditions and half under partial enrichment by adding stainless steel enclosures. All MA groups showed impaired Cincinnati water maze performance with no significant effects of rearing condition. In the Morris maze, the MA-25 group showed impaired spatial acquisition, reversal, and small platform learning. Enrichment significantly improved Morris maze acquisition in all groups but did not interact with treatment. The male MA-25 group was also impaired on probe trial performance after acquisition and on small platform trials. A narrow window of MA treatment (P11-15) induces impaired path integration learning irrespective of dose within the range tested but impairments in spatial learning are dependent on dose. The results demonstrate that a narrower exposure window (5 days) changes the long-term effects of MA treatment compared to longer exposures (10 days).

Neonatal (+)-methamphetamine exposure in rats alters adult locomotor responses to dopamine D1 and D2 agonists and to a glutamate NMDA receptor antagonist, but not to serotonin agonists

“…One in vitro study noted that the activation of NMDA receptors produced more toxicity in brain slices from younger rats (PD 21 ± 2) than from adults relative to other glutamate receptor subtypes (Sanganahalli et al 2006). We have demonstrated that PD 11–20 Meth exposure results in enduring deficits in Cincinnati water maze (CWM) learning (Grace et al 2010; Vorhees et al 2008, 2009). This maze assesses route-based egocentric learning, a form of navigation that relies on the use of self-movement cues and signposts to determine location within a given space (Byrne, 1982; di Fiore & Suarez, 2007).…”

“…Developmental Meth exposure in rats also causes weight reductions, elevated physiological stress and learning and memory deficits (Grace et al 2008; Vorhees et al 1994, 2007, 2008, 2009; Williams et al 2002, 2003 a , b , c ). The most sensitive exposure period for these effects is post-natal days (PD) 11–20, an interval that corresponds to late second to third trimester in humans based on neurogenesis rates across species (Clancy et al 2001, 2007 a , b ; Rice & Barone, 2000).…”

Dopamine depletion in either the dorsomedial or dorsolateral striatum impairs egocentric Cincinnati water maze performance while sparing allocentric Morris water maze learning

“…One day prior to CWM testing, animals were tested for swimming ability in a 244 cm long × 15 cm wide × 51 cm high water filled (38 cm deep) straight channel for 4 consecutive trials with a maximum time limit of 2 min/trial (Herring et al, 2008, Vorhees et al, 2008). Straight channel swimming served three functions: (a) to acclimate animals to swimming, (b) to teach that escape was possible by climbing on the submerged platform at the opposite end of the channel, and (c) to determine if animals had comparable swimming ability.…”

“…The CWM is a nine-unit multiple T water maze (21 ± 1°C) as described previously (Vorhees, 1987, Vorhees et al, 1991, Vorhees et al, 2008). Animals had to locate a submerged escape platform; the room was illuminated with infrared lighting in order to eliminate visual cues; a video camera was mounted above the maze sensitive to light in the infrared range and fed to a monitor in another room.…”

Dorsal striatal dopamine depletion impairs both allocentric and egocentric navigation in rats

“…One day prior to CWM testing, animals were tested for swimming in a 244 cm long × 15 cm wide × 51 cm high water filled (38 cm deep) straight channel for 4 consecutive trials with a maximum time limit of 2 min/trial (Herring et al, 2008;Vorhees et al, 2008)). Straight channel swimming served three functions: (a) swimming acclimation, (b) to teach that escape was possible by climbing on the submerged platform at the opposite end of the channel, and (c) to determine if all animals had comparable swimming ability.…”