Previous work has shown that individual differences in locomotor activity in an inescapable novel environment can predict acquisition of amphetamine self-administration. The current study examined whether individual differences in approach to novelty in a free choice test could also predict amphetamine self-administration. Further, the current study examined whether individual differences in either free choice or inescapable novelty tests could predict responding for a nondrug reinforcer (sucrose) in the presence and absence of amphetamine. Male and female rats were first tested for their response to free choice novelty (playground maze and novelty-induced place preference tests) and inescapable novelty. They were then tested for acquisition of sucrose-reinforced responding, amphetamine-induced changes in maintenance of sucrose-reinforced responding, and amphetamine self-administration. Based on the inescapable novelty test, acquisition of sucrose-reinforced responding was more rapid in male high responders (HR) compared to low responders (LR). This effect in males did not generalize to females. None of the novelty tests predicted the ability of amphetamine to decrease sucrose-maintained responding. However, using the inescapable novelty test, both male and female HRs self-administered more amphetamine than LRs within the dose range tested (0.03-0.16mg/ kg/infusion). Neither the playground maze nor the novelty-induced place preference test predicted amphetamine self-administration. These results indicate that responses to free choice novelty and inescapable novelty predict different components of amphetamine-induced behavior. O 2001 Lippincott Williams & Wilkins.

Compulsive smoking is a worldwide public health problem. Although research has confirmed the importance of associative learning processes in nicotine addiction, therapies targeting nicotine-associated cues still have a high relapse rate. Most theories conceptualize nicotine as an ‘outcome’ that reinforces behaviors and/or changes the affective value of stimuli. Albeit important, this view does not capture the complexity of associative processes involved in nicotine addiction. For example, nicotine serves as a conditional stimulus acquiring new appetitive/affective properties when paired with a non-drug reward. Also, nicotine functions as an occasion setter that participates in higher-order associative processes that likely permit a more pervasive influence of conditioned cues that are resistant to typically cue-exposure therapy techniques. Finally, nicotine appears to amplify the salience of other stimuli that have some incentive value resulting in enhanced nicotine selfadministration and conditioned reinforcement processes. Future smoking intervention strategies should take into consideration these additional associative learning processes.

Novelty seeking and sensation seeking are constructs useful in predicting human risk-taking behaviors. This predictive relation purportedly reflects some rewarding aspect of experiencing novelty. Research has confirmed this assumption. Rats display an increase in preference for an environment that has been differentially paired with novel stimuli. The physiological mechanisms mediating this rewarding effect of novelty involve the neurotransmitter dopamine, whereas those controlling novelty seeking do not. The mechanisms involved in drug seeking and reward show parallel dissociations. This concordance between novelty and drug-abuse research suggests that novelty and drug stimuli may interact in biologically and behaviorally meaningful ways. Indeed, preliminary research examining cocaine and novelty and published work with amphetamines support this suggestion. There is clear need for further systematic research on novelty reward and related processes at all levels of analysis: genetic, biological, behavioral, and social.

In a sample of 208 Holtzman-descended albino rats, we found evidence with 4 measures of conditioning (freezing, defecation, side crossing, and nose crossing) that a single 2-s, 1.0-mA immediate shock could condition fear to a context (Experiments 1, 2, and 4). When we reduced the shock intensity to 0.5 mA, we obtained a complete immediate-shock conditioning deficit according to all measures in Experiment 3 and to all but the defecation measure in Experiment 4. Results suggest two conclusions: (a) Differences in shock potency between laboratories may help explain discrepant findings about whether immediate shock supports contextual conditioning; (b) theories of contextual conditioning need a mechanism that permits that conditioning to result from immediate shock.Recently, considerable interest has developed about understanding the neural and behavioral processes mediating one-trial context fear conditioning (e.g.,

Extracellular vesicles (EVs), which express a repertoire of cargo molecules (cf. proteins, microRNA, lipids, etc.), have been garnering a prominent role in the modulation of several cellular processes. Here, using both non‐human primate and rodent model systems, we provide evidence that brain‐derived EV (BDE) miRNA, miR‐29a‐3p (mir‐29a), is significantly increased during chronic methamphetamine (MA) exposure. Further, miR‐29a levels show significant increase both with drug‐seeking and reinstatement in a rat MA self‐administration model. We also show that EV‐associated miR‐29a is enriched in EV pool comprising of small EVs and exomeres and further plays a critical role in MA‐induced inflammation and synaptodendritic damage. Furthermore, treatment with the anti‐inflammatory drug ibudilast (AV411), which is known to reduce MA relapse, decreased the expression of miR‐29a and subsequently attenuated inflammation and rescued synaptodendritic injury. Finally, using plasma from MUD subjects, we provide translational evidence that EV‐miR29a could potentially serve as a biomarker to detect neuronal damage in humans diagnosed with MA use disorder (MUD). In summary, our work suggests that EV‐associated miR‐29a‐3p plays a crucial role in MUD and might be used as a potential blood‐based biomarker for detecting chronic inflammation and synaptic damage.