Effects of MDMA, methamphetamine and methylphenidate on repeated acquisition and performance in rats

Abstract

Repeated-acquisition procedures that include performance controls for effects not specific to acquisition permit the assessment of drug effects on learning on a within-subject, within-session basis. Despite the advantages of this methodology, few studies have examined effects of psychomotor stimulants on repeated acquisition in rodents. The purpose of the present study was to investigate the effects of methylenedioxymethamphetamine (MDMA, 0.3-10 mg/kg), methamphetamine (MA, 0.1-3 mg/kg) and methylphenidate (MPD,1-17 mg/kg) using repeated-acquisition procedures with performance controls in rats using a touch-screen apparatus. Rats were presented a 2 × 3 array of stimuli using a computer touch-screen and nose-pokes to target locations within the array were reinforced. In the acquisition component, the correct location changed across sessions, whereas during the performance component, the correct location was constant across sessions. All three drugs reduced accuracy of responding to target locations in a dose-dependent fashion. None of the compounds enhanced learning at any dose. MPD and MA produced significant disruptions of acquisition accuracy only at doses that also disrupted performance, but the 3 mg/kg dose of MDMA impaired acquisition of target responding without affecting performance. The selective impairment of acquisition found in the present study adds to the evidence of learning and memory disruption produced by acute MDMA administration and raise questions about the mechanisms for these actions.

Repeated Acquisition in the Morris Swim Task: Effects of Methylenedioxymethamphetamine, Methamphetamine, and Methylphenidate

“…However, MDMA did not produce selective effects on acquisition of repeated chains in monkeys, as learning was impaired only at doses that also produced performance impairments (Thompson et al, 1987). In contrast, Galizio et al (2009) found selective effects of MDMA, but only non-selective effects of MPD and MA using a RAP procedure in rats. These findings were precisely the opposite of those reviewed above in monkeys and pigeons in which MPD and MA both produced effects that were selective to acquisition and MDMA had only non-selective effects.…”

“…Specifically, the RAP procedure used by Galizio et al (2009) required rats to make a single nose-poke response to a particular location on a touchscreen to produce food reinforcement rather than a sequence of responses. In this procedure, the correct location changed from session to session in the acquisition component (without an accompanying discriminative stimulus), but remained constant in the performance component.…”

Comparisons of 9-Tetrahydrocannabinol and Anandamide on a Battery of Cognition-Related Behavior in Nonhuman Primates

“…Subsequently, this stimulus pair appeared in every 10th trial of all sessions and served to identify nonselective motoric effects versus selective effects on learning when the effects of drugs were studied (cf. Galizio et al, 2009).…”

Blockade of 5-HT2 Receptor Selectively Prevents MDMA-Induced Verbal Memory Impairment

“…Two interesting possibilities include direct and indirect activation of postsynaptic 5-HT 2A and 5-HT 1A receptors, respectively. It is clear from animal studies that 5-HT 2A receptors mediate learning and memory processes (Galizio et al, 2009;Kay et al, 2010;Trigo et al, 2008); however, it is not completely obvious whether 5-HT 2A receptor drugs achieve their facilitating and impairing effects through agonism, antagonism or inverse agonism (Meneses, 2002). Still, there seems to be some consensus that a 5-HT 2A blockade not only improves learning, but reverses poor memory consolidation conditions associated with, among others, dysfunctional serotonergic neurotransmission (Meneses, 2007a, b) as well.…”