Conditioned taste aversion from neostigmine or methyl-naloxonium in the nucleus accumbens

Taylor, K.M. Mark, G.P. Hoebel, B.G. Conditioned taste aversion from neostigmine or methyl-naloxonium in the nucleus accumbens Physiol Behav 00(00):000–000, 2011. An opioid antagonist injected in the nucleus accumbens of a morphine-dependent rat will lower extracellular dopamine and release acetylcholine (ACh), as also seen in opiate withdrawal. It was hypothesized that raising extracellular ACh experimentally would be aversive as reflected by the induction of a conditioned taste aversion. Rats were implanted with cannulas aimed above the nucleus accumbens (NAc) for injection of the opiate antagonist methyl-naloxonium in morphine-dependent animals or neostigmine to increase ACh in drug naïve animals. Experiment 1 in addicted rats showed that local morphine withdrawal by local injection of methyl-naloxonium paired with the taste of saccharin induces a conditioned taste aversion. Experiment 2 in non-addicted rats demonstrated the same learned aversion after local administration of the cholinergic agonist neostigmine in the NAc. These results suggest that ACh released in the NAc during opiate withdrawal contributes to the dysphoric, aversive state characteristic of withdrawal. This accumbens system is implicated in the mechanism for generating the memory of an aversive event that is expressed as learned taste aversion.

► Morphine withdrawal increases Ach release in the nucleus accumbens (NAc).
► Local morphine withdrawal in the NAc induces conditioned flavor aversion.
► Local increases in ACh in the NAc induces conditioned flavor aversion.
► Increased ACh in the NAc is aversive and may be a factor in drug withdrawal.