Cocaine self-administration in mice with forebrain knock-down of trpc5 ion channels

Abstract

Canonical transient receptor potential (TRPC) channels are a family of non-selective cation channels that play a crucial role in modulating neuronal excitability due to their involvement in intracellular Ca2+ regulation and dendritic growth. TRPC5 channels a) are one of the two most prevalent TRPC channels in the adult rodent brain; b) are densely expressed in deep layer pyramidal neurons of the prefrontal cortex (PFC); and c) modulate neuronal persistent activity necessary for working memory and attention. In order to evaluate the causal role of TRPC5 in motivation/reward-related behaviors, conditional forebrain TRPC5 knock-down (trpc5-KD) mice were generated and trained to nose-poke for intravenous cocaine. Here we present a data set containing the first 6 days of saline or cocaine self-administration in wild type (WT) and trpc5-KD mice. In addition, we also present a data set showing the dose-response to cocaine after both groups had achieved similar levels of cocaine self-administration. Compared to WT mice, trpc5-KD mice exhibited an apparent increase in self-administration on the first day of cocaine testing without prior operant training. There were no apparent differences between WT and trpc5-KD mice for saline responding on the first day of training. Both groups showed similar dose-response sensitivity to cocaine after several days of achieving similar levels of cocaine intake.

DAT isn’t all that: cocaine reward and reinforcement require Toll-like receptor 4 signaling

“…Sample sizes, although appropriate for relative studies, were generally too small to test variance; however, in instances where an unpaired two-tailed t-test was used, there were no differences in variances. No statistical methods were used to pre-determine sample sizes, but our sample sizes are similar to those reported in previous publications 9 , 10 , 17 , 19 , 21 , 22 , 24 , 25 , 27 . Data collection and quantification was performed blinded whenever possible; final analyses were not performed blind to the conditions of the experiments.…”

“…Self-administration procedures were performed in operant conditioning chambers equipped with two nose-poke portals located on opposite walls and an infusion pump system 22 . Chambers were modified for sucrose self-administration mounting liquid-dispensing spigots above both ports for mice to freely lick.…”

“…Mice were implanted with chronic intravenous jugular catheters, as previously described 22 . Animals were individually housed and returned to the colony room.…”

Mechanisms of activation of nucleus accumbens neurons by cocaine via sigma-1 receptor–inositol 1,4,5-trisphosphate–transient receptor potential canonical channel pathways

“…TRPC subtypes 4 and 5 are expressed in the rodent nAcc at low and moderate levels, respectively [52], and have been implicated in cocaine-triggered motivation/reward-directed behaviors [53, 54]. Rats lacking a functional trpc4 gene showed reduced cocaine self-administration [54]; mice with selective trpc5 knock-down in the forebrain exhibited increased cocaine self-administration on the first day of testing, although were similar to wild-type mice during the maintenance phase of self-administration [53]. We report here that TRPC are critical for cocaine-triggered amplification of IP 3 /ATP-dependent Ca 2+ responses and membrane potential changes in D 1 -expressing nAcc neurons.…”

TRP Channels Regulation of Rho GTPases in Brain Context and Diseases

“…The mammalian TRPC subfamily can be divided into two subgroups based on the percentage of identity between their sequences: (1) TRPC1/TRPC2/TRPC4/TRPC6 and (2) TRPC3/TRPC6/TRPC7. (Wu et al, 2019), Cerebellar ataxia (Dulneva et al, 2015) Aberrant spine remodeling/morphology due to deregulation of CaMKII/Tiam1 axis TRPC5 Substance abuse (Pomrenze et al, 2013) -Excitotoxicity (Phelan et al, 2013) Rac1 and DR-2-mediated regulation of RhoA TRPC6 Glioma (Ding et al, 2010). AD (Lessard et al, 2005;Feng, 2017) -Salcedo et al, 2017;Chen et al, 2019), glutamatergic toxicity (Schattling et al, 2012), SCI (Gerzanich et al, 2009) Rac1-mediated induction of NADPH oxidase and ROS production TRPM7 IS (Chen et al, 2015), Neuroblastoma (Middelbeek et al, 2015) IS: RhoA upregulation and subsequent induction of cell death.…”