Self-Administration Chamber Components

• Mouse chamber
• Two nose poke apertures
• Two cue lights in the apertures
• One pellet dispenser
• Infusion pump
• Frequency tone
• Shock grid
• Shocker (optional)

Mouse Chamber

• The chamber is made of aluminum frame and acrylic walls
• Interaction panel color: default black; other colors is also available per user request
• Other sidewall colors: clear
• Chamber interior dimension (custom dimensions are available):
  • Mouse – 18 x 18 x 20 cm (width x depth x height)
  • Rat – 26 x 26 x 25 cm (width x depth x height)
• Removable grid floor
  • Mouse rod diameter: 4mm, spacing 5 mm
  • Rat rod diameter: 6mm, spacing 10mm
• The look & feel is like the pictures. The chamber control box is outside of the cubicle to eliminate the power light inside the cubicle

Two Levers

• Two levers are made of stainless steel and mounted on the interaction panel
• Width: 1.6 cm for rats and 1 cm for mice

Two Nose-poke Apertures

• Two nose poke apertures are mounted on the interaction panel, 1 cm above the floor
• Nose poke aperture dimension: 1.3 x 1.2 x 1.2 cm width x height x depth
• Each aperture is equipped with an infrared sensor capable of detecting the insertion of the animal’s nose
• Nose poke behaviors are used to determine the infusion reward or pellet reward

Two Cue Lights

• Each aperture is equipped with a cue light of configurable colors (white, red, green or blue)
• The light on/off is controlled by the program

Pellet Dispenser

• The pellet dispenser is controllable by the program. It delivers a pellet to the food receptacle given a certain condition. The sensor on the receptacle detects animal nose pokes for food.
• 20 mg pellet dispenser is the default choice (tested with pellets from Bio-Serv).
• 45 mg pellet dispenser is also available

Intravenous (IV) Drug Infusion

• Syringe pump interior diameter 12 mm
• Configurable pump speeds 0.5 – 60 RPM
• Configurable single infusion and maximum infusion amount
• Vascular access harness
• Tether kit for mouse
• Most infusion parts are from Instech Laboratories

Frequency tone

• A speaker per chamber
• Frequency tone – 100-20,000Hz frequency; volume 1-130dB 
• Independent sound frequency and volume control for each chamber

Shocker (optional)

• Shock current from 0.1 to 4.0 mA in 0.1 mA steps, programmable control
• “Start/stop“ is controlled by software or manually

Control boxes

• Each chamber unit has one control box that controls the operations of the corresponding self-administration chamber.

Main controller

• Up to 16 control boxes – each self-administration chamber has one control box that controls its operations
• The main controller connects to up to 16 chamber control boxes via wireless communication. The wireless eliminates many cable connections between the main controller and all (up to 16) chamber control boxes
• The main controller connects to the PC via a USB (RS-232) cable and communicates with Maze Engineers Self-Administration software (Conduct Self-Administration) on the PC

Software Implementation

• The Conduct Self-Administration software is used to configure and run experiments
• The software allows the protocol setting per chamber or per group so that both control and treatment (drug) groups can be tested simultaneously with the same or different parameters.
• The software supports up to 16 chambers simultaneously
• The software allows chambers to start/stop and run independently
• Have implemented many reward models including the probability model
• Collaborate closely with the user on software enhancements

Frequently Asked Questions

Documentation

Introduction

The Self-Administration Chamber is an operant behavioral assay popular in assessing reward-seeking and addiction behaviors (see also Self-Administration Runway). Drug abuse and addiction studies in humans are often based on empirical research (for digital healthcare tools visit ConductScience Digital Health), which does not provide a complete understanding of the underlying mechanisms and factors leading to these behaviors. Animal studies of self-administration, allow overcoming the ethical hurdles and also minimize the effect of individual differences associated with human studies.

The transition to drug addiction, in previously voluntary users, is a developmental-learning association taking place at the neural levels similar to behaviors associated with highly motivated reward-seeking (Everitt, & Robbins, 2005; Lewis, 2017). The Self-Administration Chamber task allows the investigation of instrumental reinforcers in promoting drug taking and seeking behaviors. The chamber consists of a simple set-up of levers and light cues along with the optional reward dispenser (in addition to the reinforcers) placed in a sound-attenuated cubicle. The subject is trained to associate lever press with drug administration, which is then used to evaluate the reinforcing effects of drugs. While the development of drug addiction has a neural basis, other factors such as social pressure and influence (Piña, Namba, Leyrer-Jackson, Cabrera-Brown, & Gipson, 2018) and comorbidity of mental illnesses (Volkow, 2001) also contribute to drug abuse. Social influences can be assessed using multiple Self-Administration Chambers, while mental illness paradigms can be achieved by combining mental illness models. The Self-Administration Chamber also comes equipped with electrified grid flooring which can be used to combine fear-learning protocols with self-administration tasks (see also Fear-Conditioning Chamber).

Automation of the protocols can be achieved using the Conductor Software. Other rodent operant assays include the IDED Operant Chamber, Attentional Set Shifting (IDED) Chamber, and Operant Conditioning Chamber (see Operant Chamber Packages). 

Apparatus and Equipment

The Self-Administration Chamber is an acrylic chamber with an overall dimension of 26 × 26 × 30 cm (mouse model has a dimension of 18 × 17 × 25 cm). The side walls are made of clear acrylic, while the remaining two walls are made of aluminum. The chamber comes with pairs of portlight (available in yellow, red, or green light) and retractable levers. The pellet/liquid receptacle (pellet dispenser or lick-o-meters) is placed in between the levers. The option to include an optic sensor to detect nose pokes is also available. The chamber also comes equipped with a removable electric grid floor and a removable feces and urine tray for easy cleaning. The grid flooring has rods having a diameter 6 mm and a spacing of 5 mm (the model has the diameter of a rod 4 mm and spacing 5 mm), and the shock intensity can be varied between 0.1 to 4 mA in 0.1 mA steps. The shock generator is placed outside the chamber. The chamber is placed within a sound-attenuating chamber (50 × 40 × 40 cm) that comes equipped with a speaker, a house light, a circulation fan, and a syringe pump system. The syringe pump system consists of a variable speed syringe pump, vascular access harness, and a tether kit for the animal.

Training Protocol

Clean the apparatus and the testing chamber prior to beginning the sessions and in between trials to prevent the influence of any lingering stimuli on the performances. Multiple animals can be tested at a time. However, testing conditions should be maintained for the groups throughout the sessions. The Self-Administration Chamber task requires food or liquid restrictions before sessions to motivate the subjects to complete the task.

Self-Administration Chamber task protocols vary depending on the requirements of the investigation. The following are the common approaches to the task (Thomsen, & Caine, 2005)

• Food restricted animals are initially trained with food rewards and then with the intravenous drug administration as a reinforcer in the absence of food reward.
• Food restricted animals are initially trained with food rewards and then with the intravenous drug administration as a reinforcer with food freely available.
• Animals are directly trained using intravenous drug reinforcement without any prior operant training. 

Following is a sample protocol for self-administration tasks using a lever manipulandum.

Food-Shaping Trials

Following familiarization with experimenter handling and the testing room, place the subject in the Self-Administration Chamber. Begin training the subject to press the lever on a fixed ratio 1 schedule using the food reinforcers. Perform one session for one hour or until 20 reinforcements have been consumed daily. Repeat trials on a fixed ratio 2 schedules. Conclude food-shaping trials when the subject achieves stable response criterion on either lever for both schedules. Follow the food-shaping trials with catheter placement surgery (for surgical tools click here).

Acquisition and Training Trials

Following the rest period, post-surgery, begin acquisition trials for drug self-administration on a fixed ratio 1 schedule. Begin each session with a priming injection of the drug. Reinforce each lever press with drug administration accompanied by the flashing of the stimulus light. Follow the lever-press with a time-out (lights turned off) of 30 seconds of no activity or reinforcement.  Perform each session for 180 minutes with a preset maximum number of injections. Conclude acquisition trials once the subject meets the predetermined acquisition criteria of minimum self-administration and active to inactive lever press ratio over 3 consecutive sessions.

Begin training sessions using a fixed ratio 2 schedule and unlimited reinforcers. Conduct each session for 90 minutes until a stable baseline for drug intake is established across three consecutive sessions.

Dose-Response Test Trials

Conduct test trials similar to the training session, with the exception that the priming dose is the same as the dose being tested. Test each dose independently over consecutive days. End the phase with saline-only trials.

Extinction Trials

Present the subject with both active and inactive levers. However, program both levers to have no consequences when pressed. Observe extinction behaviors for about 30 to 90 minutes.

Relapse-Reinstatement Test Trials

Ideally, relapse-reinstatement sessions should be performed after a forced abstinence period. The following protocol uses three reinstatement induction conditions: conditioned stimuli, stress, and drug infusion.

Follow the extinction trials by a conditioned stimuli-induced reinstatement test in the absence of drug infusion. During the first 30 minutes, present the conditioned stimuli (cue light associated with drug infusion), non contingently, for 20 seconds. Follow this with another 30 minutes of contingent presentation of the conditioned stimuli (2 seconds) on active lever presses on a fixed ratio 1 schedule. End the phase with a foot shock followed immediately by 30 minutes period of observation of nonreinforced responding. Begin the next reinstatement period (30 minutes) with a noncontingent drug infusion.

Literature Review

Investigation of the abuse-potential of 25 N-NBOMe drug

Seo et al. (2019) investigated the rewarding and reinforcing effects of the emerging psychoactive drug 2-(2,5-dimethoxy-4-nitrophenyl)-N-(2-methoxybenzyl) ethanamine (25 N-NBOMe) in male C57BL/6 J mice and male Sprague-Dawley rats. Drug treatment groups included 25 N-NBOMe hydrochloride groups, methamphetamine hydrochloride group (positive control), and saline group (negative control). Drugs were administered intraperitoneally at 10 ml/kg for C57BL/6 J mice and intravenously at 0.1 ml/kg/infusion to Sprague-Dawley rats. Rats were tested in the Self-Administration task following recovery from the catheter placement surgery. Drug doses assessed included, 0.01, 0.03, and 0.1 mg/kg/infusion of 25 N-NBOMe and 0.05 mg/kg/infusion methamphetamine. The sessions were performed using a fixed ratio 1 schedule (drug delivery over 4 seconds period) over 7 consecutive days and lasted 2 hours each. Both 25 N-NBOMe at 0.01 mg/kg/infusion and methamphetamine at 0.05 mg/kg/infusion significantly increased the number of infusions compared to the saline group on days 4, 6, and 7, and days 2 to 7, respectively. Additionally, methamphetamine resulted in significantly increased infusions in session 3 in comparison to the 25 N-NBOMe groups. Further assessment was performed using mice in the Conditioned Place Preference test. Following habituation and baseline testing, the mice underwent drug conditioning on days 4 to 11. During this period, mice were injected either with 25 N-NBOMe (0.3, 1, and 3 mg/kg, i.p.) or methamphetamine (1 mg/kg, i.p.) in one chamber on even days. On odd days they were administered with saline in the other chamber. At a dose of 3 mg/kg, 25 N-NBOMe, and 1 mg/kg methamphetamine, mice were observed to display enhanced conditioned place preference in comparison to the saline controls. However, no such significant impact was observed at 0.3 mg/kg and 1 mg/kg doses of 25 N-NBOMe. 

Investigation of the effect of social defeat on cocaine self-administration

Arena, Covington, DeBold, and Miczek (2019) investigated the effects of intermittent versus continuous social stress in male C57BL/6J mice in the drug self-administration assay. Subjects were divided into intermittent social defeat stress and continuous social defeat stress group. Both groups underwent resident-intruder (see Resident-Intruder Chamber) stress treatment for 10 consecutive days using male CFW mice.  Intermittent stress involved exposing mice to the aggressive resident through a perforated cage for five minutes, followed by direct interaction with the resident (maximum 5 minutes) and ending with another 5 minutes of exposure to the resident through the perforated cage. Following the treatment, mice were returned to their single housing. Continuous stress treatment was similar to the intermittent stress protocol, except that the intruder mice were kept in the resident aggressor’s cage separated by a perforated wall for the rest of the day. The subjects were paired with a new aggressor throughout the course to prevent habituation. Approximately 17 days following the stress treatment, subjects were evaluated in the cocaine self-administration task. Mice were trained to self-administer 0.3 mg/kg/infusion cocaine on a fixed ratio 1 (FR1) schedule for a week. Drug dose testing was performed using FR1 schedule with descending doses 0.1, 0.03, 0.01, 0.003, and 0.001 mg/kg/infusion. Each dose was tested for 2 consecutive days. The intermittent stress group displayed a significant increase in cocaine self-administration on acquisition day 1 (in comparison to controls) though no interaction between stress and cocaine dosage could be observed. In the continuous stress group, two distinct cocaine-taking phenotypes were observed; high-responders that had an average infusion of 23 mg/kg/session and low-responders with an average infusion of 3 mg/kg/session during days 2–7 of acquisition. In comparison to the modest increase in cocaine self-administration of the intermittent stress group, continuous social defeat stress resulted in either increased or attenuated cocaine infusion. This behavior of the continuous social defeat group was comparable to that observed during the sucrose preference test.

Investigation of the relation between drug-relapse vulnerability and decision-making deficits

Cocker, Rotge, Daniel, Belin-Rauscent, and Belin (2019) investigated whether escalated cocaine intake impacted decision-making and if decision-making behaviors can be predictive of drug relapse. Baseline decision-making performances of adult male Sprague‐Dawley rats were assessed in the rodent version of the Iowa Gambling Task (IGT) in a 5-hole operant chamber (see 5CSRTT Chamber). Rats were trained with 4 active nose-poke holes in the following order, two free‐choice training sessions, four forced‐choice sessions, and two consecutive free‐choice sessions (the second session introduced rats to higher incentives of 2 pellets in the first half). Following training, the gambling task was commenced with 2 holes being the advantageous choice while the other two being disadvantageous. The advantageous choice resulted in one sugar pellet and time‐out punishments of 6 or 12 seconds (probability of 0.5 and 0.25, respectively), while the disadvantageous choice resulted in 2 sugar pellets and time-out punishment of 222 or 444 seconds (probability of 0.5 and 0.25, respectively). Following baseline performances, rats were subjected to cocaine self-administration assay in the Self-Administration Chamber using an infusion dose of 250 μg/100 μL/5.7 s) under a fixed ratio 1 schedule (20 s time‐out period). Once rats had acquired cocaine self-administration, they were exposed to 12 hours of extended access sessions for 19 days to induce escalation of cocaine intake. On completion of the self-administration assay, subjects underwent forced abstinence for a week, following which relapse/extinction and reinstatement session was performed. Additionally, decision-making performances in the gambling task were evaluated 1 day, 1 week, and 1 month following the end of long access to cocaine sessions. In the gambling task, only a subset of rats displayed significant impairment in decision making. These rats also displayed increased vulnerability to relapse, as observed by the increased instrumental responding during the extinction period.

Investigation of the effects of extended use of methamphetamine on recognition memory

Male Sprague-Dawley rats were used to investigate the memory impairments resulting from the extended self-administration of methamphetamine. Following recovery from catheter placement surgery, an infusion dose of 20 μg/50 μl bolus was administered. Active lever presses were accompanied by 5 seconds of light and tone cues. The extended self-administration protocol involved a 1 hour per day meth hydrochloride self-administration for 7 days, followed by 14 days of 6 hours of access per day to the drug. Yoked controls received saline. Following approximately 1 week of abstinence, rat performances were evaluated in the Novel Object Recognition task. Rats were first allowed 3 minutes to familiarize themselves with two identical objects, 90 minutes following which they were presented with one of the familiar objects and a novel object for 3 minutes. Long-term memory analysis was performed 24 hours later using the familiar object and a new novel object. Performances between the drug-treated and controls were similar during the familiarization phase of the Novel Object Recognition task; however, significant differences in performances could be observed during novelty testing. Controls were observed to spend a significant amount of time with the novel object and have robust novel recognition memory, as opposed to the meth group. However, no significant difference in the distance traveled, and approach scores could be observed between the groups. (Scofield et al., 2015)

Investigation of the effect of environmental enrichment on methylphenidate self-administration

Alvers, Marusich, Gipson, Beckmann, and Bardo’s (2012) investigation found that rats raised in enriched environments had lower susceptibility to methylphenidate in comparison to those raised in isolation, though at lower doses. Male Sprague-Dawley rats were either housed in group settings with enrichment objects (EC) or maintained in isolation in the solid side and back walls (IC). Rats underwent catheter placement surgery at approximately postnatal day 55 and were allowed a week of recovery. Methylphenidate self-administration acquisition was performed using lever-press conditioning at a dose of 0.3 mg/kg/infusion (0.1 ml/infusion, 5.9 s/infusion). Rats initially underwent auto-shaping sessions paired with daily self-administration sessions (fixed ratio 1 schedule) for 7 consecutive days. At the end of the week, only fixed ratio sessions were continued. The fixed-ratio schedules progressed from a fixed ratio of one to five. Each ratio schedule was allocated 3 consecutive days except a fixed ratio 5 schedule, which was allocated 7 days. The dose-effect of methylphenidate was assessed under two schedules: fixed ratio and progressive ratio. Under fixed ratio 5 schedule, methylphenidate doses of 0.03, 0.056, 0.1, 0.56, and 1.0 mg/kg/infusion were presented in either ascending or descending order. Each dose was offered for 3 consecutive sessions. At the end of the trials, subjects were evaluated using saline substitution for 7 consecutive days. In the progressive ration schedule, the response requirement was increased exponentially. The subjects were first presented with a 0.3 mg/kg/infusion for three consecutive days, following which doses of 0.03, 0.1, 0.3, and 1.0 mg/kg/infusion (either ascending or descending order) were presented for 3 consecutive days each. At the end of the trials, subjects were evaluated using saline substitution for 7 consecutive days. During the acquisition phases of both experimental conditions, infusion rates declined as the fixed ratio increased. Under the fixed ratio condition, a significant difference between EC and IC rats in infusion numbers was observed only at 0.056 mg/kg/infusion, with IC rats having higher mean infusions than the EC rats. Further, inactive lever presses were observed to occur more at lower doses than higher ones. Similarly, under fixed-ratio conditions, IC rats had significantly higher infusions than EC at 0.03 mg/kg/infusion dose of methylphenidate. Further, inactive lever presses were highest at the dose of 0.3 mg/kg/infusion. It was also observed that the number of infusions was higher at 0.1, 0.3, and 1.0 mg/kg/infusion when doses were presented in descending order. Under both experimental conditions, EC response to saline substitution reflected rapid extinction in comparison to the IC rats. 

Data Analysis

The following observations can be made in the Self-Administration Chamber Task,

• Number of infusions
• Number of active lever presses/nose-pokes
• Number of inactive lever presses/nose-pokes

Strengths and Limitations

Strengths

The Self-Administration Chamber can be used with either nose-poke or lever manipulandum. While the nose-poke system is considered more natural for rodents, the use of lever is equally effective. The lever system allows retraction of the levers, which can be helpful during the acquisition phase or non-activity phase. The chamber also allows the opportunity to use either liquid or food rewards. The chamber also comes equipped with a speaker, light, and electric grid flooring, which allows different combinations of conditioning cues. The use of electric grid flooring is useful in evaluating stress and fear-induced reward-seeking or drug abuse behaviors. The chamber assay, unlike the Self-Administration Runway, does not include a locomotory element.

Limitations

Improper post-surgery care can potentially affect self-administration performances. For protocols that require pretraining using appetitive rewards, subjects need to be placed on liquid or food restrictions. Thus, the subject’s appetitive motivation needs to be maintained during trials. Improper handling of the subject can induce stress in the subject, which can, in turn, affect performances. Factors such as age, strain, species, and sex can also impact performances. Changes in the context or food reward may affect performances.

Summary

• The Self-Administration Chamber is an operant chamber used in reward-seeking and drug abuse research.
• The chamber allows the use of either nose-poke or lever press manipulandum. 
• The apparatus comes with an electrified-shock grid that can be used to evaluate stress- or fear-induced drug-seeking. Audio and light cues are also available.
• The task doesn’t involve significant locomotory activity, unlike the Self-Administration Runway.
• Performances in the apparatus may be affected by the animal’s lack of appetitive motivation.

References

1. Alvers, K. M., Marusich, J. A., Gipson, C. D., Beckmann, J. S., & Bardo, M. T. (2012). Environmental enrichment during development decreases intravenous self-administration of methylphenidate at low unit doses in rats. Behavioural Pharmacology, 23(7), 650–657. doi:10.1097/fbp.0b013e3283584765
2. Arena, D. T., Covington, H. E., DeBold, J. F., & Miczek, K. A. (2019). Persistent increase of I.V. cocaine self-administration in a subgroup of C57BL/6J male mice after social defeat stress. Psychopharmacology. doi:10.1007/s00213-019-05191-6
3. Cocker, P. J., Rotge, J.-Y., Daniel, M.-L., Belin-Rauscent, A., & Belin, D. (2019). Impaired decision making following escalation of cocaine self-administration predicts vulnerability to relapse in rats. Addiction Biology. doi:10.1111/adb.12738
4. Everitt, B. J., & Robbins, T. W. (2005). Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nature Neuroscience, 8(11), 1481–1489. doi:10.1038/nn1579
5. Klebaur, J. E., Phillips, S. B., Kelly, T. H., & Bardo, M. T. (2001). Exposure to novel environmental stimuli decreases amphetamine self-administration in rats. Experimental and Clinical Psychopharmacology, 9(4), 372–379. doi:10.1037/1064-1297.9.4.372
6. Lewis, M. (2017). Addiction and the Brain: Development, Not Disease. Neuroethics, 10(1), 7–18. doi:10.1007/s12152-016-9293-4
7. Piña, J. A., Namba, M. D., Leyrer-Jackson, J. M., Cabrera-Brown, G., & Gipson, C. D. (2018). Social Influences on Nicotine-Related Behaviors. International Review of Neurobiology. doi:10.1016/bs.irn.2018.07.001
8. Rocha, B. A., Ator, R., Emmett-Oglesby, M. W., & Hen, R. (1997). Intravenous Cocaine Self-Administration in Mice Lacking 5-HT1B Receptors. Pharmacology Biochemistry and Behavior, 57(3), 407–412. doi:10.1016/s0091-3057(96)00444-3
9. Scofield, M. D., Trantham-Davidson, H., Schwendt, M., Leong, K.-C., Peters, J., See, R. E., & Reichel, C. M. (2015). Failure to Recognize Novelty after Extended Methamphetamine Self-Administration Results from Loss of Long-Term Depression in the Perirhinal Cortex. Neuropsychopharmacology, 40(11), 2526–2535. doi:10.1038/npp.2015.99
10. Seo, J.-Y., Hur, K.-H., Ko, Y.-H., Kim, K., Lee, B.-R., Kim, Y.-J., … Jang, C.-G. (2019). A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents. Brain Research Bulletin. doi:10.1016/j.brainresbull.2019.07.002 
11. Thomsen, M., & Caine, S. B. (2005). Chronic Intravenous Drug Self-Administration in Rats and Mice. Current Protocols in Neuroscience. doi:10.1002/0471142301.ns0920s32
12. Volkow, N. D. (2001). Drug Abuse and Mental Illness: Progress in Understanding Comorbidity. American Journal of Psychiatry, 158(8), 1181–1183. doi:10.1176/appi.ajp.158.8.1181