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Effects of laterodorsal tegmental nucleus cholinergic neuron lesions on cocaine self-administration in rats

Wednesday, October 26, 2011 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center




  • S Steidl
  • H Wang
  • M Morales
  • RA Wise


The laterodorsal tegmental (LDTg) and pedunculopontine tegmental (PPTg) nuclei provide the only known source of cholinergic input to the ventral tegmental area (VTA). Here we used a selective neurotoxin, constructed by conjugation of diphtheria toxin to urotensin-II peptide, to test the role of mesopontine ACh neurons in cocaine self-administration. Lesions of LDTg ACh neurons significantly reduced cocaine intake across days, primarily by increasing the latency to initiate lever pressing for cocaine. Thus, rats with LDTg ACh lesions are less responsive to cues that, in the past, have reliably predicted the availability of cocaine, and that normally trigger short-latency responding. Priming injections of cocaine (10 mg/kg, i.p.) and pretreatment with the anxiolytic drug diazepam (1 mg/kg, i.p.), which eliminates ambivalence in cocaine-rewarded runway behavior, decreased response latencies in LDTg ACh-lesioned rats. Once responding was initiated in response to priming injections of cocaine, rats regulated their intake, varying response rates inversely with dose per injection. Rats that initiated responding without priming injections tended to respond slightly more slowly than in all other conditions. We hypothesize that the increased latencies are due to loss or attenuation of VTA ACh elevations that usually accompany signaled cocaine availability.

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