Dorsal hippocampus inhibition disrupts acquisition and expression, but not consolidation, of cocaine conditioned place preference.

Abstract

Cocaine abusers may experience drug craving upon exposure to environmental contexts where cocaine was experienced. The dorsal hippocampus (DHC) is important for contextual conditioning, therefore the authors examined the specific role of the DHC in cocaine conditioned place preference (CPP). Muscimol was used to temporarily inhibit the DHC and was infused before conditioning sessions or tests for CPP to investigate acquisition and expression of cocaine CPP, respectively. To investigate consolidation, rats received intra-DHC muscimol either immediately or 6 hr after conditioning sessions. Inhibition of DHC, but not the overlying cortex, disrupted acquisition and expression of cocaine CPP. It is interesting to note that there was no effect of post-conditioning DHC inhibition. The findings suggest that the DHC is important for both acquisition and recall, but not consolidation, of context-cocaine associations.

Inhibition of Hippocampal β-Adrenergic Receptors Impairs Retrieval But Not Reconsolidation of Cocaine-Associated Memory and Prevents Subsequent Reinstatement

“…dHipp inactivation or lesions disrupt context-dependent fear memory expression (Kim and Fanselow, 1992;Corcoran and Maren, 2001) and disrupt cocaine-induced CPP expression (Meyers et al, 2003(Meyers et al, , 2006. Mice lacking NE are unable to express contextinduced fear (Murchison et al, 2004) or drug-associated memories (Jasmin et al, 2006;Olson et al, 2006).…”

“…Moreover, norepinephrine (NE) and b-AR activation within dHipp are critical for contextual fear memory retrieval, but not for fear expression alone (Murchison et al, 2004). The dHipp is activated by drug-associated cue exposure in both rodents (Neisewander et al, 2000;Hearing et al, 2010) and humans (Hermann et al, 2006), and dHipp inactivation prevents context-driven drug seeking and reinstatement (Fuchs et al, 2005;Meyers et al, 2006). Despite evidence that dHipp is involved in memory retrieval and reinstatement, it remains unclear whether dHipp b-AR activation is required for drug-associated memory retrieval and subsequent druginduced reinstatement.…”

Adolescent Rats Find Repeated Δ9-THC Less Aversive Than Adult Rats but Display Greater Residual Cognitive Deficits and Changes in Hippocampal Protein Expression Following Exposure

“…While the hippocampus does play a role in the acquisition of contextual conditioning to various drugs (Meyers et al, 2006;Sharifzadeh et al, 2006), forming a link between lesser place aversion to THC in adolescent rats and hippocampal proteomic changes is difficult given that proteomic analysis occurred 3 weeks after place conditioning and at a time when the adolescent rats had reached adulthood. Analysis of the proteomic effects of acute cannabinoid treatment in adolescent and adult rats would clearly be an interesting follow-up study and might usefully examine nonhippocampal sites implicated in cannabinoid-reward, such as mesolimbic regions (Zangen et al, 2006).…”

Altered Neural Cholinergic Receptor Systems in Cocaine-Addicted Subjects

“…The dorsal hippocampus is required for contextual conditioning during cocaine administration. For example, lesions of the dorsal hippocampus disrupt both the acquisition and expression of cocaine conditioned place preference in the rodent (Meyers et al, 2006) and Crombag et al (2008) have posited a function for a serial relationship between the dorsal hippocampus, basolateral amygdala, dorsal striatum, and dorsal medial PFC in context-induced drug reinstatement. Contextual learning processes are mediated, at least in part, by cholinergic receptors and the hippocampus has among the highest concentrations of ACh in the CNS.…”