A similar pattern of neuronal Fos activation in 10 brain regions following exposure to reward- or aversion-associated contextual cues in mice

Abstract

JOHNSON, Z.V., A.A. REVIS, M.A. BURDICK, AND J.S. RHODES. A similar pattern of neuronal Fos activation in 10 brain regions following exposure to reward-or aversion-associated contextual cues in mice. PHYSIOL BEHAV 00(0) 000-000, 2009 -Relapse triggered by drug-paired cues is a major obstacle for successful treatment of drug abuse. Patterns of brain activation induced by drugpaired cues have been identified in human and animal models, but lack of specificity poses a serious problem for craving or relapse interpretations. The goal of this study was to compare brain responses to contextual cues paired with a rewarding versus an aversive stimulus in a mouse model to test the hypothesis that different patterns of brain activation can be detected. Mice were trained to associate a common environmental context with an intraperitoneal injection of saline, lithium choride or cocaine. After measuring each animal for conditioned place preference or aversion, mice were reexposed to the context (CS+ or CS−) in absence of the reinforcer to analyze patterns of Fos expression in 10 brain regions chosen from previous literature. Levels of Fos in the cingulate cortex, paraventricular thalamic nucleus, paraventricular hypothalamic nucleus, and dentate gyrus differed in CS+ versus CS− groups, but the direction of the differences were the same for both lithium chloride (LiCl) and cocaine reinforcers. In the cingulate cortex, Fos was positively correlated with degree of place preference for cocaine or aversion to LiCl whereas in the periaqueductal gray the relationship was positive for LiCl and negative for cocaine. Results confirm Fos responses to reward-or aversionpaired cues are similar but specificity is detectable. Future studies are needed to comprehensively establish neuroanatomical specificity in conditioned responses to drugs as compared to other reinforcers.

The MEK inhibitor SL327 blocks acquisition but not expression of lithium-induced conditioned place aversion: a behavioral and immunohistochemical study

“…Pre-conditioning preference times did not significantly differ between experimental groups, being 525±24 for SL327 (0 mg/kg)+lithium (0 mg/kg), 511±14 for SL327 (25 mg/kg)+lithium (0 mg/kg), 525±27 for SL327 (50 mg/kg)+lithium (0 mg/kg), 553±16 for SL327 (0 mg/kg) + lithium (150 mg/kg), 557 ± 11 for SL327 (25 mg/kg)+lithium (150 mg/kg), and 542±22 s/900 for SL327 (50 mg/kg)+lithium (150 mg/kg) groups (F(1, 29)= 1.86, NS). In agreement with previous observations (Acquas et al 1989;Acquas and Di Chiara 1994;Ventura et al 2007;Johnson et al 2010), lithium elicited a negative side preference shift from 553±16 to 380±28 s/900 at the post-conditioning test (p<0.05). Repeated measures, threeway ANOVA of the effects of SL327 and lithium, with preference times (pre-and post-conditioning) as repeated dependent measures and with pre-treatment (SL327 0, 25, and 50 mg/kg) and treatment (lithium 0 and 150 mg/kg) doses as independent measures, revealed a significant effect of time (F 1, 29 =9.64, p<0.004) and significant treatment by time (F 1, 29 =14.97, p <0.0005) and pre-treatment by treatment by time (F 2, 29 =3.68, p<0.037) interactions.…”

Capturing and Manipulating Activated Neuronal Ensembles with CANE Delineates a Hypothalamic Social-Fear Circuit

“…Previous studies also identified brain regions in which brief behaviors of opposite valences activated spatially intermingled populations of Fos+ neurons (Johnson et al, 2010; Kollack-Walker and Newman, 1995; Kovacs, 1998; Lin et al, 2011; Veening et al, 2005; Wu et al, 2014; Xiu et al, 2014). Thus, tools that can determine whether the same or different ensembles of neurons are activated and express Fos in different contexts or behaviors, and can manipulate the activated neurons to determine their causal functions are highly desired.…”

Parameters for abolishing conditioned place preference for cocaine from running and environmental enrichment in male C57BL/6J mice

“…injections in a volume of 10 ml/kg. Dose was chosen based on the literature and was prepared according to the salt not the base form [12, 13, 43, 44]. …”

“…We used the same unbiased procedure as previously published by our lab [12, 13, 43] based on Cunningham’s apparatus and experimental design [45] and as previously detailed in our other work [12, 13, 43]. Within each treatment group, mice were counterbalanced with respect to the conditioned stimulus (CS+GRID or CS+HOLE) and experienced cocaine on GRID (CS+GRID) or cocaine on HOLE (CS+HOLE) texture and saline on the alternate texture.…”

“…Moreover, each group serves as the other group’s learning control, because both groups learned to associate one texture with cocaine and the alternate texture with saline. This is important because as compared to using a control in which all animals receive saline on both textures, the experience of learning itself could bias preferences for the textures [12, 13, 43]. …”