A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Abstract

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.

Automatic aspects of response selection remain unchanged during high‐dose alcohol intoxication

“…Even though the latter have repeatedly been the subject of investigation, there is no general consensus on whether or not AUD patients show general and uniform changes in S-R binding: On the one hand, it has repeatedly been shown that AUD patients display enhanced associations and pavlovian instrumental transfer for alcohol-associated stimuli. 55,56 With respect to neutral (ie, nonalcohol-related) stimulus processing, there are however much fewer findings, and they tend to rather point into the opposite direction. In line with this, individuals with AUD seem to show reduced proactive inference 57 and potentially reduced attentional processing of environmental stimuli.…”

“…Ideally, such investigations would include different groups, like moderate drinkers, regular binge‐drinkers, and AUD patients. Even though the latter have repeatedly been the subject of investigation, there is no general consensus on whether or not AUD patients show general and uniform changes in S‐R binding: On the one hand, it has repeatedly been shown that AUD patients display enhanced associations and pavlovian instrumental transfer for alcohol‐associated stimuli 55–56 . With respect to neutral (ie, nonalcohol‐related) stimulus processing, there are however much fewer findings, and they tend to rather point into the opposite direction.…”

Sex differences in the amplification of responding to an alcohol-predictive cue by an alcohol-associated context

“…Every other day (i.e. Monday, Wednesday, Friday) rats were given 24-hour access to 15% EtOH and water via a 100 ml graduated cylinder and 500 ml bottle that were placed onto the home cage lids (Maddux, Lacroix, & Chaudhri, 2014;Simms et al, 2008;Wise, 1973). On Tuesday, Thursday, Saturday, and Sunday, EtOH cylinders were replaced with water bottles (procedure adapted from Sparks, Sciascia, Ayorech, & Chaudhri, 2014).…”