Social stress and escalated drug self-administration in mice II. Cocaine and dopamine in the nucleus accumbens

Abstract

Rationale Social defeat stress results in escalation of cocaine taking and long-term neural adaptations in rats. How the intensity and timing of social defeat stress determine these effects, particularly in mice, have not been well characterized. Objective This study investigated the effects of mild vs. moderate intensities and durations of social stress on intravenous cocaine self-administration as well as on dopamine (DA) release in nucleus accumbens shell (NAcSh) by using in vivo microdialysis. Methods Adult male CFW mice experienced 10 days of social defeat stress, either mild (15 attack bites in ca. 1.8 min) or moderate (30 attack bites in ca. 3.6 min), and compared to controls that were handled daily. Subsequently, the socially stressed mice were assessed for either (1) intravenous cocaine self-administration, using several unit doses (0, 0.3, 0.6, 1.0 mg/kg/infusion) under limited access conditions, or (2) neural sensitization, as determined by in vivo microdialysis of DA in the NAcSh in response to acute d-amphetamine challenge. Results Social defeat stress resulted in escalated cocaine self-administration in both mild and moderate socially stressed groups. In addition, social defeat stress led to increased DA release after d-amphetamine challenge. Conclusions These data suggest that both mild and moderate socially stressed mice exhibit increased cocaine taking compared to controls, and this increase is associated with escalated dopaminergic responses in the NAcSh.

Prevention and reversal of social stress-escalated cocaine self-administration in mice by intra-VTA CRFR1 antagonism

“…As previously described (Han et al 2015; Miczek and O’Donnell 1978), we used a resident-intruder paradigm for social defeat. Mice in the stressed groups were exposed to ten daily brief episodes of social defeats.…”

“…The custom apparatus used for cocaine self-administration was as described previously (Han et al 2015; Yap and Miczek 2007). A panel equipped with cue lights and two nose-poke operanda was inserted vertically into the home cage of the animal.…”

“…After the acquisition, mice were subsequently tested under an FR1 schedule with 0.3 mg/kg/infusion unit dose of cocaine, which was indicated as an optimal dosage to identify the stress effects on escalated cocaine intake in mice (Han et al 2015). In experiment 2, mice were pretreated with CP 376,395 (0, 5 and 15 mg/kg, i.p.)…”

Alpha-PVP induces the rewarding effect via activating dopaminergic neuron

“…), were placed in a stereotaxic apparatus. A microdialysis probe (D-I-6-01; 0.22 mm outer diameter, 1 mm membrane length; Eicom Co., Ltd., Kyoto, Japan) was implanted into the nucleus accumbens shell at the following coordinates: AP: + 1.76 mm, ML: + 0.5 mm relative to bregma and DV: − 5.0 mm from the skull (Han et al, 2015). The probes were secured to the skull using dental acrylic.…”

“…Such effects of α-PVP could be involved in the drug-induced CPP in mice. Chronic cocaine administration increases extracellular DA levels in the nucleus accumbens (Pettit and Justice, 1991;Han et al, 2015). Methamphetamine increases extracellular DA levels in the brain, by facilitating the release from presynaptic nerve terminals and inhibiting the reuptake from synaptic effect (Nakajima et al, 2004).…”