Competition between ethanol-induced reward and aversion in place conditioning

Abstract

Previous place conditioning studies in mice have shown that injection of ethanol immediately before a conditioned stimulus (CS+) produces conditioned preference, whereas injection of ethanol immediately after CS+ produces conditioned aversion. In the present experiments, we examined the learning that occurs when ethanol is injected in "ambiguous" procedures that provide the opportunity for both types of conditioning. When ethanol was given midway through the CS (Experiments 1 and 2) or both before and after the CS (Experiment 3), the direction of place conditioning was the same as when mice were exposed only to whichever contingency occurred first (a primacy effect). That is, injection of ethanol in the middle of the CS conditioned aversion, whereas injection both before and after the CS conditioned preference. Because these results support the idea that ethanol elicits both aversive and rewarding effects, they are most consistent with conditioning theories that conceptualize unconditioned stimuli (USs) as events that can activate multiple representational components.

Proximal ethanol pretreatment interferes with acquisition of ethanol-induced conditioned place preference

“…Given that outcome, one might have expected the combination of a pretreatment injection 30 min (or less) before the US injection to produce an enhanced conditioned place preference. The failure to see temporal summation in the present situation is at odds with the previous observation of summation with two closely spaced ethanol injections when the first injection occurred just before CS exposure and the second injection was given 5 min later (Cunningham et al, 2003b). In that case, magnitude of place preference was enhanced, as would be expected when the CS is paired with a larger ethanol dose (Cunningham et al, 1992;Risinger & Oakes, 1996).…”

“…For example, we suggested that ethanol pre-exposure reduced conditioned place aversion produced by post-CS ethanol injection because it reduced the aversiveness of the rapid transition from the sober to the intoxicated state. However, an explanation of the present results based on direct interference with ethanol's rewarding effect seems unlikely given the previous finding of reward summation across two injections given 5 min apart (Cunningham et al, 2003b). Rather, the present findings seem more reasonably explained by assuming that ethanol pretreatment directly interfered with the formation of an association between the CS and ethanol US 5 min later.…”

Ethanol-induced conditioned place preference, but not aversion, is blocked by treatment with d-penicillamine, an inactivation agent for acetaldehyde

“…The place-conditioning paradigm can measure either the positive reinforcing or aversive properties of the same drug, depending on subtle procedural differences during conditioning. Indeed, Cunningham et al (1997) demonstrated that the temporal relationship between the injection of ethanol and the conditioned stimulus (CS) is critical to determine whether mice will show CPP or CPA (Cunningham et al 1997(Cunningham et al , 2003Cunningham and Henderson 2000). The direction of the conditioning response produced by ethanol depends on the interstimulus interval (Cunningham et al 1997).…”

“…The grid floor was constructed from 2.3-mm stainless steel rods mounted 6.4 mm apart on acrylic rails; the holed floor consisted of perforated stainless steel sheet metal (16 gauge) containing 6.4 mm round holes on 9.5 mm staggered centers. This combination of floor textures was selected based on previous studies showing that drug-naive control mice spend about half their time on each floor type during preference test (Cunningham et al 1992(Cunningham et al , 2003. All experiments (conditioning and preference test) were recorded through a computerized video tracking system (SMART; Spontaneous Motor Activity Recording & Tracking.…”

“…Ethanol induces behavioral stimulation (Pohorecky 1977;Sanchis-Segura et al 1999a;Font et al 2001), locomotor sensitization (Masur and Boerngen 1980;Phillips et al 1994;Miquel et al 2003), oral self-administration Koechling and Amit 1994), conditioned place preference (CPP) (Cunningham et al 1992;Risinger and Oakes 1996) and conditioned place aversion (CPA) (Cunningham et al 1997(Cunningham et al , 2003Cunningham and Henderson 2000).…”