Handling blocks expression of conditioned place aversion but not conditioned place preference produced by ethanol in mice

Previous findings implicate opioid receptors in the expression of the conditioned rewarding and aversive properties of ethanol. We have recently reported that the conditioned rewarding effect of ethanol is mediated by opioid receptors in the ventral tegmental area (VTA). We attempted to determine whether VTA opioid receptors also mediate the expression of the conditioned aversive properties of ethanol. However, the magnitude of conditioned place aversion (CPA) was not consistent with our previous findings and prevented us from making definitive conclusions. We hypothesized that the handling required to make intracranial infusions in mice alters the expression of CPA, but not conditioned place preference (CPP). Therefore, non-operated animals underwent a Pavlovian conditioning procedure for either ethanol CPA or CPP. Just before testing, half of the animals were held by the scruff of the neck to mimic intracranial infusion handling. Animals conditioned for CPA did not express CPA if they were handled. However, animals conditioned for CPP exhibited robust CPP, regardless of handling. These findings provide additional evidence that the conditioned rewarding and aversive effects of ethanol are mediated by different neural mechanisms.