Comparison of monoamine and corticosterone levels 24 h following (+)methamphetamine, (+/–)3,4‐methylenedioxymethamphetamine, cocaine, (+)fenfluramine or (+/–)methylphenidate administration in the neonatal rat

Abstract

We have previously shown that neonatal administration of (+/-)3,4-methylenedioxymethamphetamine and (+)fenfluramine produce deficits in spatial and path integration learning, whereas (+)methamphetamine causes deficits in spatial learning. Conversely, cocaine and (+/-)methylphenidate have no effect on either form of learning following neonatal administration. The purpose of the present study was to determine whether corticosterone and/or monoamine levels were changed following subcutaneous administration of 10 mg/kg (+)methamphetamine, (+/-)3,4-methylenedioxymethamphetamine, (+)fenfluramine, (+/-)methylphenidate or cocaine every 2 h (total of four injections) on postnatal day 11. Twenty-four hours after the first dose, plasma, striatum and hippocampus were collected. Corticosterone levels were increased in methamphetamine-, fenfluramine-, methylenedioxymethamphetamine-and methylphenidate-treated rats relative to levels in saline-treated rats, whereas cocaine-treated rats were unaffected. In the striatum and hippocampus, serotonin and 5-hydroxyindolacetic acid were reduced in animals treated with methylenedioxymethamphetamine or fenfluramine, compared with levels in saline controls. Dopamine levels were not changed by any of the drugs, although 3,4-dihydroxyphenylacetic acid was decreased following methylenedioxymethamphetamine or methamphetamine. Minimal effects were seen in neurotransmitter levels following injection of cocaine or methylphenidate. These data suggest that drugs that affect corticosterone and hippocampal serotonin are associated with both spatial learning and path integration deficits, and those that affect corticosterone and 3,4-dihydroxyphenylacetic acid are associated with spatial learning deficits only.

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

“…In addition, it is known that activation of D 1 receptors in other brain regions such as the medial prefrontal cortex and orbitofrontal cortex also play a role in motor inhibition (Diaz et al 2004; Heijtz et al 2007; Pellis et al 2006). Therefore, we suggest that early Meth treatment sensitizes DA D 1 receptors while desensitizing D 2 receptors (Crawford et al 2003; Schaefer et al 2006, 2008; Williams et al 2003 a ). Whether the smaller D 2 receptor change was a direct effect of Meth exposure or an indirect effect via the Meth-induced change in D 1 receptor sensitivity cannot be determined from the present data.…”

“…Less is known about the receptor alterations following early Meth exposure, as the aforementioned data are gleaned from adult rodent studies and short-term changes in DA levels are not reported to occur during PD 11–20 drug administration (Schaefer et al 2006, 2008). Interestingly, the findings in the present study indicate that the D 1 and D 2 receptors show lasting functional changes following developmental Meth treatment although we did not directly assay receptor number or affinity.…”

Developmental effects of 3,4-methylenedioxymethamphetamine: a review

“…No effects on dopamine were observed in the striatum; however, there were reductions in DOPAC seen at 6, 24, and 30 h after the first dose . The 24 h reductions in 5-HT and 5-HIAA were replicated in a subsequent study (Schaefer et al, 2006). After behavioral testing (approximately P105), the study by Broening et al (2001) examined monoamine levels in adult animals exposed to 5, 10, or 20 mg/kg twice a day of MDMA from either P1 to P10 or P11 to P20.…”

Treatment with MDMA from P11–20 disrupts spatial learning and path integration learning in adolescent rats but only spatial learning in older rats

“…A possible mechanism involving 5-HT signaling, however, does exist. First, recent data showed that after MDMA exposure on P11, hippocampal 5-HT levels drop sharply Schaefer et al 2006). Second, MDMA treatment from P11-20 increases 5-HT 1A receptor activity in the hippocampus (Crawford et al 2006).…”