Dopamine in the Dorsal Hippocampus Impairs the Late Consolidation of Cocaine-Associated Memory

Abstract

Cocaine is thought to be addictive because it elevates dopamine levels in the striatum, reinforcing drug-seeking habits. Cocaine also elevates dopamine levels in the hippocampus, a structure involved in contextual conditioning as well as in reward function. Hippocampal dopamine promotes the late phase of consolidation of an aversive step-down avoidance memory. Here, we examined the role of hippocampal dopamine function in the persistence of the conditioned increase in preference for a cocaine-associated compartment. Blocking dorsal hippocampal D1-type receptors (D1Rs) but not D2-type receptors (D2Rs) 12 h after a single training trial extended persistence of the normally short-lived memory; conversely, a general and a specific phospholipase C-coupled D1R agonist (but not a D2R or adenylyl cyclase-coupled D1R agonist) decreased the persistence of the normally long-lived memory established by three-trial training. These effects of D1 agents were opposite to those previously established in a step-down avoidance task, and were here also found to be opposite to those in a lithium chloride-conditioned avoidance task. After returning to normal following cocaine injection, dopamine levels in the dorsal hippocampus were found elevated again at the time when dopamine antagonists and agonists were effective: between 13 and 17 h after cocaine injection. These findings confirm that, long after the making of a cocaine-place association, hippocampal activity modulates memory consolidation for that association via a dopaminedependent mechanism. They suggest a dynamic role for dorsal hippocampal dopamine in this late-phase memory consolidation and, unexpectedly, differential roles for late consolidation of memories for places that induce approach or withdrawal because of a drug association.

Activation of Glycogen Synthase Kinase-3 Mediates the Olfactory Deficit-Induced Hippocampal Impairments

“…The step-down passive avoidance task was carried as described to evaluate the long-term memory that related with the hippocampus of the rats [38,39]. The testing apparatus consisted of an acrylic box (30×30×30 cm) with a floor made of parallel stainless steel grid (1.0 mm in diameter) spaced 1 cm apart.…”

Dopamine D1/D5 receptors in the dorsal hippocampus are required for the acquisition and expression of a single trial cocaine-associated memory

“…The needle was left in place for an additional minute after infusion to allow for diffusion and to prevent reflux. The doses employed of each compound (1.5 lg/ll for SCH 23390, 0.1 lg/ll for muscimol and 1.5 lg/ll for eticlopride hydrochloride) were proven to be effective by different studies Kramar et al, 2014;Lintas et al, 2011;Rossato et al, 2009). At the end of each experiment, cannula placement was verified by infusion of 1 ll of 4% methylene blue.…”

“…If during the pretest phase an animal failed to spend at least 90 s in each compartment it was excluded from the study (3 animals were excluded for this reason, less than 1%). A cocaine dose of 20 mg/kg was used for all the experiments (Kramar et al, 2014).…”

“…If this learning is perceived as ''novel'', a signal is conveyed through polysynaptic pathways to the ventral tegmental area (VTA) dopamine (DA) neurons (Lisman & Grace, 2005;Luo, Tahsili-Fahadan, Wise, Lupica, & Aston-Jones, 2011), which are able to detect novelty signals and changes their firing pattern in response. VTA DA neurons innervate the hippocampus (Gasbarri, Sulli, & Packard, 1997), and hippocampal DA neurotransmission has been shown to modulate synaptic plasticity and memory (Bernabeu, Cammarota, Izquierdo, & Medina, 1997;Kramar, Chefer, Wise, Medina, & Barbano, 2014;Lemon & ManahanVaughan, 2006;Lisman & Grace, 2005;Rossato, Bevilaqua, Izquierdo, Medina, & Cammarota, 2009). However, much less is known about the involvement of the hippocampus in the acquisition, consolidation and expression of the memory for appetitive learning tasks and, in particular, drug-associated experiences.…”

“…Cocaine also elevates DA levels in the hippocampus (Kramar et al, 2014), a structure that has been shown to regulate the release of DA in the nucleus accumbens core and shell (Peleg-Raibstein & Feldon, 2006). In addition, cocaine enhances hippocampal long-term potentiation (LTP) (Thompson, Gosnell, & Wagner, 2002).…”