Brief Reportγ-Aminobutyric Acid Cells with Cocaine-Induced ΔFosB in the Ventral Tegmental Area Innervate Mesolimbic Neurons
Section snippets
Animals
Experiments were conducted in male Sprague-Dawley rats (280–340 g, Janvier, France) group-housed with food and water ad libitum. Procedures were performed in accordance with European Directives.
Surgery
Rats underwent unilateral stereotaxic surgery under ketamine (87 mg/kg)/xylazine (13 mg/kg) anesthesia. Stereotaxic coordinates relative to bregma (8) were: tVTA, anteroposterior (AP) = −6.3 mm, lateral (L) = +1.6 mm, vertical (V) = −7.6 mm, 6° lateral angle; VTA, AP = −5.2 mm, L = +1.4 mm, V = −7.8 mm,
Results
The tVTA location was defined by cocaine-induced FosB/ΔFosB staining (Figures 1A–1C and Figure S1 in Supplement 1). The tVTA-restricted BDA injections resulted in the presence of a heavy plexus of BDA-positive fibers in the anterior and posterior VTA and in the substantia nigra pars compacta (SNC) (Figures 1D and 1E). Co-staining with TH revealed that a majority of VTA dopamine cells displayed somatic appositions from BDA-positive fibers and boutons (Figures 1F–1J). Because synaptic contacts
Discussion
After cocaine exposure, ΔFosB is expressed in GABA neurons of the tVTA that send dense efferents to the midbrain dopaminergic system. This system influences numerous physiological functions (10) and is implicated in the etiology or treatment of neurological or psychiatric diseases, such as Parkinson's, schizophrenia, mood disorders, and drug abuse (11, 12). The activity of the VTA dopamine neurons is known to be under GABAergic influences from both VTA inputs and intra-VTA GABA interneurons (13
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2021, Pharmacology Biochemistry and BehaviorCitation Excerpt :The RMTg represents relatively pure GABA cell population (Jhou et al., 2009a; Kaufling et al., 2009; Olson and Nestler, 2007; Perrotti et al., 2005) with high levels of MOR immunoreactivity and mRNA (Galaj et al., 2020; Jalabert et al., 2011; Jhou et al., 2009a, 2012) and high levels of the neuropeptide nociception (Jhou et al., 2012). RMTg GABA neurons send dense projections to the VTA and substantia nigra zona compacta (SNc) (Jhou et al., 2009b; Kaufling et al., 2010), where they form synapses with approximately 80% of DA neurons (Balcita-Pedicino et al., 2011). Matsui and colleagues examined inhibitory GABA postsynaptic currents (IPSCs) evoked by selective optical stimulation of GABA projections from the VTA, NAc, or RMTg and found that inhibition of IPSCs induced by MOR agonists was pathway-dependent (Matsui et al., 2014).