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“Dopaminergic projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc) mediate the behavioral and motivational effects of many drugs of abuse, including nicotine. Repeated intermittent administration of these drugs, a pattern often associated with initial drug exposure, sensitises the reactivity of dopamine (DA) neurons

in this pathway, enhances the locomotor behaviors the drugs emit, and promotes their pursuit and self-administration. Here we show that activation of nicotinic acetylcholine receptors (nAChRs) in the VTA, but not the NAcc, is essential for the induction of locomotor sensitisation GS-1101 mw by nicotine. Repeated intermittent nicotine exposure (4 × 0.4 mg/kg, base, i.p., administered over 7 days), a regimen leading to long-lasting locomotor sensitisation, also produced upregulation of nAChRs in the VTA, but not the NAcc, in the hours following the last exposure injection. Functional nAChR upregulation was observed selectively in DA but not GABA neurons in the VTA. These effects were followed by long-term potentiation of excitatory

inputs to these cells and increased nicotine-evoked DA overflow EX527 in the NAcc. Withdrawal symptoms were not observed following this exposure regimen. Thus, intermittent activation and upregulation by nicotine of nAChRs in DA neurons in the VTA may contribute to the development of behavioral sensitisation and increased liability for nicotine addiction. “
“Two main neuronal pathways connect facial whiskers to the somatosensory cortex in rodents: (i) the lemniscal pathway, which originates in the brainstem principal trigeminal nucleus and is relayed

in the ventroposterior thalamic nucleus and (ii) the paralemniscal pathway, originating in the spinal trigeminal nucleus and relayed Erastin in vitro in the posterior thalamic nucleus. While lemniscal neurons are readily activated by whisker contacts, the contribution of paralemniscal neurons to perception is less clear. Here, we functionally investigated these pathways by manipulating input from the whisker pad in freely moving mice. We report that while lemniscal neurons readily respond to neonatal infraorbital nerve sectioning or whisker contacts in vivo, paralemniscal neurons do not detectably respond to these environmental changes. However, the paralemniscal pathway is specifically activated upon noxious stimulation of the whisker pad. These findings reveal a nociceptive function for paralemniscal neurons in vivo that may critically inform context-specific behaviour during environmental exploration.