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

• Published in: Brain research Vol. 1123; no. 1; pp. 51 - 59
• Main Authors: Mark, Gregory P., Kinney, Anthony E., Grubb, Michele C., Zhu, Xiaoman, Finn, Deborah A., Mader, Sarah L., Berger, S. Paul, Bechtholt, Anita J.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 06.12.2006; Amsterdam Elsevier; New York, NY
• Subjects: Acetylcholine; Addiction; Analysis of Variance; Animals; Behavior, Addictive - metabolism; Biological and medical sciences; Cholinergic system; Cocaine - administration & dosage; Cocaine-Related Disorders - metabolism; Dose-Response Relationship, Drug; Drug addictions; Feeding Behavior - drug effects; Feeding Behavior - physiology; Male; Medical sciences; Mesolimbic dopamine system; Microinjections; Muscarinic Agonists - administration & dosage; Muscarinic receptor; Neuropharmacology; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Oxotremorine - administration & dosage; Pharmacology. Drug treatments; Pirenzepine; Progressive ratio; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - metabolism; Reward; Self Administration; Toxicology; Mesolimbic dopamine system; Addiction; Progressive ratio; Muscarinic receptor; Cholinergic system; Acetylcholine; Pirenzepine; Rat; Psychotropic; Central nervous system; Self administration; Encephalon; Cholinergic receptor; Drug of abuse; Dopamine; CNS stimulant; Rodentia; Basal ganglion; Catecholamine; Nucleus accumbens; Chemotherapy; Vertebrata; Mammalia; Treatment; Animal; Neurotransmitter; Cocaine
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.09.029

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 M 1 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.