Rationale: Among the various experimental protocols that have been used to measure drug reward in laboratory animals, conditioned place preference (CPP) has been one of the most popular. However, a number of controversial issues have surrounded the use of this experimental protocol. Objective: The present review provides a theoretical overview of some critical issues relevant to CPP. The advantages and limitations of CPP are also covered. Results: Based on modern and traditional theoretical formulations of Pavlovian conditioning, CPP appears to refl ect a preference for a context due to the contiguous association between the context and a drug stimulus. Within this theoretical framework, it seems clear that CPP measures a learning process that is fundamentally distinct from drug self-administration. The main advantages of CPP are that it: (1) tests animals in a drugfree state; (2) is sensitive to both reward and aversion; (3) allows for simultaneous determination of CPP and locomotor activity; (4) is adaptable to a variety of species; (5) typically yields dose-effect curves that are monophasic rather than biphasic; and (6) has utility in probing the neural circuits involved in drug reward. The main limitations of CPP are that it: (1) is subject to interpretation based on the notion of novelty seeking; (2) is cumbersome for providing the graded dose-effect curves needed for answering some pharmacological questions; (3) is diffi cult to interpret when animals prefer one context prior to drug conditioning; and (4) lacks face validity as an experimental protocol of drug reward in humans. Conclusion: Despite some limitations, CPP provides unique information about the rewarding effect of contextual cues associated with a drug stimulus.

Rats and mice have a tendency to interact more with a novel object than with a familiar object. This tendency has been used by behavioral pharmacologists and neuroscientists to study learning and memory. A popular protocol for such research is the object-recognition task. Animals are first placed in an apparatus and allowed to explore an object. After a prescribed interval, the animal is returned to the apparatus, which now contains the familiar object and a novel object. Object recognition is distinguished by more time spent interacting with the novel object. Although the exact processes that underlie this 'recognition memory' requires further elucidation, this method has been used to study mutant mice, aging deficits, early developmental influences, nootropic manipulations, teratological drug exposure and novelty seeking.

Abstract:Rationale: In Pavlovian conditioning research, nicotine is typically conceptualized as the unconditioned stimulus (US) that becomes associated with an exteroceptive conditioned stimulus (CS). This research has not explored the possibility that nicotine can also function as a CS. Objectives: The present research examined whether nicotine served as a CS for the presence (CS+) or absence (CS-) of sucrose and started defi ning its specifi city. Methods and results: Rats trained in the CS+ condition had nicotine (0.4 mg/ kg, base) paired intermittently with brief access to sucrose. Intermixed were saline sessions without sucrose. Nicotine acquired the ability to evoke goal tracking. This conditioned response (CR) decreased across extinction sessions. The CR was sensitive to nicotine dose (ED 50 =0.113 mg/kg) and administration to testing interval; 0-min and 100-min delays produced no CR. The CS properties were specifi c to nicotine in that amphetamine and bupropion substitution was incomplete. Rats in the CS-condition received similar discrimination training except that sucrose was paired with saline. Nicotine also served as a CS-; the saline state CS+ acquired control of goal tracking. Mecamylamine, but not hexamethonium, blocked nicotine's ability to serve as a CS+ and CS-, indicating a role for central nicotinic acetylcholine receptors. Conclusions: Nicotine served as a signal for the presence or absence of sucrose. The extinction, CS-, and substitution results eliminated a psycho motor stimulant account. The conceptualization of nicotine as a CS suggests novel empirical research in which a drug acquires additional inhibitory and/ or excitatory value based on other outcomes present during its effects.

Methamphetamine (METH) is a frequent drug of abuse in U.S. populations and commonly associated with psychosis. This may be a factor in frequent criminal justice referrals and lengthy treatment required by METH users. Persecutory delusions and auditory hallucinations are the most consistent symptoms of METH-associated psychosis (MAP). MAP has largely been studied in Asian populations and risk factors have varied across studies. Duration, frequency and amount of use as well as sexual abuse, family history, other substance use, and co-occurring personality and mood disorders are risk factors for MAP. MAP may be unique with its long duration of psychosis and recurrence without relapse to METH. Seven candidate genes have been identified that may be associated with MAP. Six of these genes are also associated with susceptibility, symptoms, or treatment of schizophrenia and most are linked to glutamatergic neurotransmission. Animal studies of pre-pulse inhibition, attenuation of social interaction, and stereotypy and alterations in locomotion are used to study MAP in rodents. Employing various models, rodent studies have identified neuroanatomical and neurochemical changes associated with METH use. Throughout this review, we identify key gaps in our understanding of MAP and suggest potential directions for future research.

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