The infralimbic medial prefrontal cortex (IL) is important for suppressing learned behavior after extinction, but whether this function extends to responses acquired through appetitive Pavlovian conditioning is unclear. We trained male, Long-Evans rats to associate a white-noise conditional stimulus (CS; 10 s; 14 presentations per session) with 10% liquid sucrose (0.2 mL per CS presentation), and recorded entries into the fluid port during the CS. The CS was presented without sucrose in subsequent extinction and test sessions. Increasing IL activity with pretest microinfusions of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 0, 0.3 nmol; 0.3 μl/side) reduced the reinstatement of CS-elicited port entries. The same result was obtained when IL neurons that expressed Channelrhodopsin-2 (ChR2) were optically stimulated during CS presentations at test (473 nm, 5 ms pulses at 20 Hz for 10.2 s, unilateral). Optical stimulation of ChR2-expressing IL neurons during CS presentations also reduced spontaneous recovery and context-induced renewal. Furthermore, optical stimulation (1) during intertrial intervals had no impact on renewal, (2) depolarized ChR2-expressing IL pyramidal neurons in vitro, and (3) preferentially increased Fos in ChR2-expressing neurons. These novel converging data highlight a critical role for the IL in suppressing the return of appetitive Pavlovian-conditioned responding following extinction.

No abstract

Varenicline, a pharmacotherapy for tobacco addiction, reduces alcohol consumption in humans and rodents. The therapeutic potential of varenicline would escalate if it also diminished conditioned responses elicited by alcohol-predictive cues, which can precipitate relapse in abstinent individuals. We investigated this application, along with the underlying neural substrates, using a robust preclinical assay in which relapse to alcohol-seeking was triggered by re-exposure to an alcohol-associated environmental context. Male, Long-Evans rats received Pavlovian conditioning sessions in which one auditory conditioned stimulus (CS+) was paired with 15% ethanol and a second conditioned stimulus (CS − ) was not. Ethanol was delivered into a port for oral consumption and port entries triggered by each CS were recorded. Extinction was then conducted in a different context where the CS+ and CS − were presented without ethanol. To stimulate relapse, both cues were subsequently presented without ethanol in the prior conditioning context. Systemic varenicline (0, 0.5 or 2.5 mg/kg; intraperitoneal) blocked context-induced relapse to alcohol-seeking without affecting the ability to make a port entry. It also reduced context-induced relapse to sucrose-seeking, but only at the 2.5 mg/kg dose. Neuropharmacological studies showed that context-induced relapse to alcohol-seeking was attenuated by bilateral microinfusion of varenicline (0.3 μl/side) into the nucleus accumbens (NAc; 0 or 3.5 μg), but not the ventral tegmental area (0, 2 or 4 μg). These data show for the first time that varenicline reduces relapse triggered by contexts that predict alcohol, and suggest that nicotinic acetylcholine receptors in the NAc are critical for this effect.

International audienceThis paper presents two studies that aim to unpack cultural variations in general social anxiety and the offensive-type of \emph{Taijin Kyofusho} (OTKS) -- a type of social anxiety characterized by the extreme fear of offending others. Cultural variations in the expression and manifestation of social anxiety are well established; however, the mechanisms underpinning this relation are unclear. The present studies use the Parallel Multiple Mediation Model to study how social anxiety and OTKS are jointly shaped by self-construal and intolerance of uncertainty. Study 1 compared Euro-Canadians and Chinese migrants in Canada. Results showed a mean group difference in OTKS, but not social anxiety, with the difference mediated by intolerance of uncertainty (IU). Study 2 tested this pattern of multiple mediations in Japanese, Chinese and Euro-Canadian cultural contexts. Results showed significant differences among these three cultural groups on both social anxiety and OTKS via multiple mediators (e.g., independent vs. interdependent self-construals and IU). Findings in both studies revealed that OTKS seems to be a psychopathology that is not specific to Japanese participants. The underlying mechanisms and processes of OTKS are also significantly different from social anxiety. Significant cultural variations in social anxiety and OTKS between Chinese vs. Japanese cultural contexts were observed in Study 2. These studies demonstrate the conceptual and empirical advantages of using more complex models to unpack the psychological mechanisms shaping cultural variations in social anxiety and OTKS

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS-stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS-are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS-as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.