CONICET | Buscador de Institutos y Recursos Humanos

Several studies have reinforced the hypothesis that drug addiction should be understood in terms of an abnormal recruitment of neural systems that usually mediate learning and memory processes. All drugs of abuse activate the mesolimbic dopaminergic system, which originates in the VTA. Recent results point dopamine from the VTA-hippocampus pathway as a key neurotransmitter in the persistence of an aversive memory when acting 12 hours after learning. The aim of this work is to evaluate if this neurobiological mechanism can be generalized to appetitive memories, specifically those related to drugs of abuse. We developed a modified conditioned place preference protocol in rats, employing cocaine, with a weak (using only one pairing between the drug and the context, which induces a 24 hours- but not 7 days-lasting memory) and a strong conditioning schedule (using three pairings, which induces a memory lasting 24 hours and 7 days). Next, we wanted to manipulate the persistence of those memories and to determine the dopaminergic mechanisms involved, if any. To achieve this, we bilaterally infuse the dorsal hippocampus with dopaminergic agonist (SKF 38393) or antagonist (SCH 23390), 12 hours after each cocaine conditioning session. Memory was evaluated at 24 hours or 7 days post-conditioning. We observed a persistent memory after SCH infusion in the weak protocol and a decreased memory after SKF infusion in the strong protocol, both results when the test was conducted after 7 days. No modifications were observed when memory was evaluated at 24 hours. Our results suggest an opposite role of dopamine in the hippocampus with regard to memory persistence, which depends on the type of memory: if it is aversive, dopamine is essential for their maintenance; if it is appetitive, dopamine might act to attenuate it.