Injection of oxotremorine in nucleus accumbens shell reduces cocaine but not food self-administration in rats

Gregory Mark, Anthony E. Kinney, Michele C. Grubb, Xiaoman Zhu, Deborah (Deb) Finn, Sarah L. Mader, S. Paul Berger, Anita J. Bechtholt

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Mesencephalic dopamine neurons form synapses with acetylcholine (ACh)-containing interneurons in the nucleus accumbens (NAcc). Although their involvement in drug reward has not been systematically investigated, these large aspiny interneurons may serve an important integrative function. We previously found that repeated activation of nicotinic cholinergic receptors enhanced cocaine intake in rats but the role of muscarinic receptors in drug reward is less clear. Here we examined the impact of local changes in muscarinic receptor activation within the NAcc on cocaine and food self-administration in rats trained on a progressive ratio (PR) schedule of reinforcement. Animals were given a minimum of 9 continuous days of drug access before testing in order to establish a stable breaking point (BP) for intravenous cocaine infusions (0.75 mg/kg/infusion). Rats in the food group acquired stable responding on the PR schedule within 7 days. On the test day, rats were bilaterally infused in the NAcc with the muscarinic receptor agonist oxotremorine methiodide (OXO: 0.1, 0.3 or 1 nmol/side), OXO plus the M1 selective antagonist pirenzepine (PIRENZ; 0.3 nmol/side) or aCSF 15 min before cocaine or food access. OXO dose dependently reduced BP values for cocaine reinforcement (- 17%, - 44% [p <0.05] and - 91% [p <0.0001] for 0.1, 0.3 and 1.0 nmol, respectively) and these reductions dissipated by the following session. Pretreatment with PIRENZ blocked the BP-reducing effect of 0.3 nmol OXO. Notably, OXO (0.1, 0.3 and 1.0 nmol/side) injection in the NAcc did not affect BP for food reward. The results suggest that muscarinic ACh receptors in the caudomedial NAcc may play a role in mediating the behavior reinforcing effects of cocaine.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalBrain Research
Volume1123
Issue number1
DOIs
StatePublished - Dec 6 2006

Fingerprint

Oxotremorine
Self Administration
Nucleus Accumbens
Cocaine
Muscarinic Receptors
Food
Injections
Reward
Interneurons
Pharmaceutical Preparations
Pirenzepine
Reinforcement Schedule
Muscarinic Agonists
Dopaminergic Neurons
Nicotinic Receptors
Cholinergic Receptors
Intravenous Infusions
Synapses
Acetylcholine
Appointments and Schedules

Keywords

  • Acetylcholine
  • Addiction
  • Cholinergic system
  • Mesolimbic dopamine system
  • Muscarinic receptor
  • Pirenzepine
  • Progressive ratio

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Injection of oxotremorine in nucleus accumbens shell reduces cocaine but not food self-administration in rats. / Mark, Gregory; Kinney, Anthony E.; Grubb, Michele C.; Zhu, Xiaoman; Finn, Deborah (Deb); Mader, Sarah L.; Berger, S. Paul; Bechtholt, Anita J.

In: Brain Research, Vol. 1123, No. 1, 06.12.2006, p. 51-59.

Research output: Contribution to journalArticle

Mark, Gregory ; Kinney, Anthony E. ; Grubb, Michele C. ; Zhu, Xiaoman ; Finn, Deborah (Deb) ; Mader, Sarah L. ; Berger, S. Paul ; Bechtholt, Anita J. / Injection of oxotremorine in nucleus accumbens shell reduces cocaine but not food self-administration in rats. In: Brain Research. 2006 ; Vol. 1123, No. 1. pp. 51-59.
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