Conditioned place preference/aversion

Preclinical studies suggest that D3 DR antagonists reduce the influence of environmental stimuli associated with nicotine, but do not reduce response to aversive stimuli or natural reinforcers. For example, smdies have shown that D3 DR antagonists reduced nicotine-conditioned place preference in rats, with no reduction in place preference to food (Le Foil et al. 2005 Pak et al. 2006) They also reduced nicotine-conditioned locomotor activity in rats (Le Loll et al. 2003 Pak et al. 2006). These results may be especially relevant to smoking cessation, because conditioning processes appear to play a large role in smoking behavior. 

Kosten, Therese A., Mindy J. Miserendino, Sandra Chi, and Eric J. Nestler. 1994. "Fischer and Lewis Rat Strains Show Differential Cocaine Effects in Conditioned Place Preference and Behavioral Sensitization but Not in Locomotor Activity or Conditioned Taste Aversion." Journal of Pharmacology and Experimental Therapeutics 269 137-44. 

Further problems are encountered with substances such as THC, where place preference can be observed over a narrow range of low doses (0.5-1 mg/kg i.p.), but where place aversion is observed at higher doses (Maldonado and Rodriguez de Fonseca 2002). Conditioned place preference has been reported with nicotine, but only after a short pretreatment with nicotine before commencing place preference conditioning (Shoaib et al. 1994). We have been unable to replicate this finding in our own laboratory (our unpublished data). 

Suzuki et al. (1991, 1993) and del Pozo et al. (1996) studied opioid-induced place preference in and Bechtholt et al. (2004) studied the effects of handling on conditioned place aversion and conditioned place preference by ethanol in mice. 

Acquas E, Di Chiara G (1994) Dl receptor blockade stere-ospecifically impairs the acquisition of drug-conditioned place preference and place aversion. Behav Pharmacol 5 555-560... 

Acquas E, Carboni E, Garau L, Di Chiara G (1990) Blockade of acquisition of drug-conditioned place aversion by 5-HT3antagonists. Psychopharmacology 100 459 163 Amalric M, Cline EJ, Martinez JL Jr, Bloom FE, Koob GF (1987) Rewarding properties of P-endorphin as measured by conditioned place preference. Psychopharmacology 91 14-19... 

Martin-Iverson MT, Reimer AR, Sharma S (1997) Unbiased cocaine conditioned place preferences (CPP) obscures conditioned locomotion, and nimodipine blockade of cocaine CPP is due to conditioned place aversions. Psychopharmacology 130 327-333... 

Acquas E, Carboni E, Leone P, Di Chiara G (1989) SCH 23390 blocks drug-conditioned place preference and place-aversion anhedonia (lack of reward) or apathy (lack of motivation) after dopamine-receptor blockade. 

Cunningham CL, Gremel CM, Groblewski PA (2006) Drug-induced conditioned place preference and aversion in mice. Nat Protoc 1(4) 1662-1670. 

In order to distinguish place preference and place aversion, place conditioning behavior can be expressed by a difference in preference pre and post conditioning, where post and pre values are the difference in time spent in the preferred and the non-preferred sides in the post-conditioning and pre-conditioning tests, respectively. Positive values indicate preference and negative values aversion (Kitaichi et al. 1996). For non-biased procedures, where animals do not show an inherent preference for either compartment, results are presented simply as a difference score (i.e., time spent in the drug-paired compartment minus time spent in the vehicle-paired compartment). 

Summing up, blockade of DA transmission impairs acquisition of place preference conditioned by appetitive as well as aversive drugs. In the case of psychostimulants this effect might be the result of a combination of an action on DA-dependent reward and on Pavlovian incentive learning. In the case of aversive drugs, which do not increase, or even decrease, DA transmission, an action on Pavlovian incentive learning is more likely. 

The administration of cannabinoid agonists can produce both rewarding and aversive/dysphoric effects in the place conditioning paradigm, depending on the dose and the experimental conditions. Thus, THC produced place preference in rats when administered at low doses and when animals were exposed to a 24-h washout period between the two THC conditioning sessions (Lepore et al. 1995). THC also... 

Kitaichi K, Noda Y, Hasegawa T, Furukawa H, Nabeshima T (1996) Acute phencyclidine induces aversion, but repeated phencyclidine induces preference in the place conditioning test in rats. Eur J Pharmacol 318 7-9... 

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