Inactivation of the paraventricular thalamus abolishes the expression of cocaine conditioned place preference in rats

Abstract

Background: The paraventricular thalamus (PVT) is rapidly becoming recognized as part of the addiction circuitry. In addition to its strong anatomical connection to most of the brain regions underlying addiction, such as the nucleus accumbens, prefrontal cortex, amygdala, and hippocampus, the PVT has recently been shown to contribute to cocaine sensitization and reinstatement. In the present study, we examined the role of the PVT in the expression of cocaine conditioned place preference (CPP).

Methods: We tested the impact of PVT inactivation by baclofen/muscimol (bac-mus) microinjection on the expression of cocaine-induced CPP in rats. Rats were implanted with guide cannulae into the PVT. Bac-mus (GABAB-GABAA agonists) or saline was injected into the PVT prior to CPP testing.

Results: Inactivation of the PVT by bac-mus prevented the expression of CPP, while placements outside the PVT did not affect CPP. Intra-PVT injections of bac-mus did not affect locomotor activity during the session.

Conclusions: In the present study, we contribute to the growing body of research supporting a role for the PVT in addiction by demonstrating that the PVT is necessary for the expression of cocaine CPP.

Keywords: Addiction; CPP; Cocaine; Inactivation; PVT.

Figure 1. Inactivation of the PVT inhibits the expression of cocaine conditioned place preference in rats

Data are expressed as mean preference score ± SEM. (A) Preference scores of rats with cannulae placements in the PVT. (B) Preference scores of rats with cannulae placements outside of the PVT. Grey bars represent animals given the vehicle dose, white bars represent animals given the low dose (0.001 nmol/nl baclofen and 0.0001 nmol/nl muscimol) of bac-mus, and black bars represent animals given the high dose (0.006 nmol/nl baclofen and 0.0006 nmol/nl muscimol) of bac-mus.*Represents a significant difference from vehicle dose (One-way ANOVA, followed by Tukey, *P≤0.05, **P≤0.01, ***P≤0.001).

Figure 2. Inactivation of the PVT does not affect locomotor activity during the test session

Data are expressed as mean ± SEM of photocell beam breaks (A). All animals had confirmed cannulae placements in the PVT. Grey bars represent animals given the vehicle dose, white bars represent animals given the low dose (0.001 nmol/nl baclofen and 0.0001 nmol/nl muscimol) of bac-mus, and black bars represent animals given the high dose (0.006 nmol/nl baclofen and 0.0006 nmol/nl muscimol) of bac-mus.*Placement of cannulae within the PVT are shown in (B) Cannula tips of “PVT hits” are represented by black dots. Cannula tips of “PVT misses” are represented by grey pluses. Note: PVA represents the anterior paraventricular nucleus.