Extracellular dopamine, acetylcholine, and activation of dopamine D1 and D2 receptors after selective breeding for cocaine self-administration in rats

Abstract

RATIONALE The LS/Kgras (LS) and HS/Kgras (HS) rat lines were generated by selective breeding for low- and high- intravenous cocaine self-administration, respectively, from a common outbred Wistar stock (Crl:WI). This trait has remained stable after 13 generations of breeding. OBJECTIVE To compare cocaine preference, neurotransmitter release, dopamine receptor activation in LS and HS rats. METHODS Levels of dopamine, acetylcholine and cocaine were measured in the nucleus accumbens (NA) shell of HS and LS rats by tandem mass spectrometry of microdialysates. Cocaine-induced locomotor activity and conditioned-place preference were compared between LS and HS rats. RESULTS HS rats displayed greater conditioned-place preference scores compared to LS, and reduced basal extracellular concentrations of dopamine and acetylcholine. However, patterns of neurotransmitter release did not differ between strains. Low-dose cocaine increased locomotor activity in LS rats, but not in HS animals; while high-dose cocaine augmented activity only in HS rats. Either dose of cocaine increased immunoreactivity for c-Fos in the NA shell of both strains, with greater elevations observed in HS rats. Activation identified by cells expressing both c-Fos and dopamine receptors was generally greater in the HS strain, with a similar pattern for both D1 and D2 dopamine receptors. CONCLUSIONS Diminished levels of dopamine and acetylcholine in the NA shell, with enhanced cocaine-induced expression of D1 and D2 receptors, is associated with greater rewarding effects of cocaine in HS rats and an altered dose-effect relationship for cocaine-induced locomotor activity.

[18F]FDG brain uptake of C57Bl/6 male mice is affected by locomotor activity after cocaine use: A small animal positron emission tomography study

“…The brain glucose metabolism reflects in part the energy required for neurotransmission, so regional abnormalities in this process provide mechanistic information on specific neurotransmitters associated with these changes (Fowler et al, 1967). After the intake of a psychostimulant drug, such as cocaine, temporally limited function changes occur in the brain (Peña et al, 2015; Ungless et al, 2001; Xu et al, 2017). The higher amounts of dopamine interacting with D1 receptors in the nigrostriatal and mesocorticolimbic projections contribute to the established psychostimulant hyperactive state, reflecting in animals as hyperlocomotion (Koob, 1992).…”

Transcriptomic effects of paternal cocaine-seeking on the reward circuitry of male offspring

“…Stronger response to cocaine (Fig. 5E ) may be a key factor leading to changes in drug susceptibility in offspring [ 40 , 45 ]. We also observed transcriptomic changes in the dHip induced by the “highly motivated” factor (Fig.…”

Sodium tanshinone IIA sulfonate protects against Aβ‐induced cell toxicity through regulating Aβ process

“…The impairment of cognitive function is the characteristic of AD. The pathological product, Aβ (the main component of amyloid plaques), acts as a central role in AD process . Aβ can aggregate to form oligomers.…”

“…The pathological product, Aβ (the main component of amyloid plaques), acts as a central role in AD process. [30][31][32][33] Aβ can aggregate to form oligomers. The Aβ oligomers are the most toxic to neuron.…”