On 2014 Nov 11, Serge Ahmed commented:

This comment is a follow-up of my previous comment about the difficulty in interpreting this study that contradicts most previous similar studies. After a careful analysis of this paper and after collecting all elements of methods “ectopically scattered” through the text, I think I finally arrived at a satisfactory explanation for why most rats preferred cocaine over sweet water in the present study. Briefly, everything was made to make access to sweet water reinforcement less direct and more difficult than access to cocaine reinforcement, thereby biasing choice towards cocaine!

More specifically, rats had to go through an unusually long chain of behavioral events before getting access to sweet water. A similar chain was not required for cocaine delivery. First, once rats turned the wheel on the operant panel, they had to cross the cage to reach a magazine on the opposite panel inside which there was a retractable drinking spout that delivered sweet water. This arrangement introduces a spatial and thus a time gap between responding and sweet water reinforcement. Both gaps are known to reduce conditioning. Second, once rats have reached the magazine, they did not have directly access to the drinking spout that delivered sweet water. They had first to insert their head into the magazine to make the retractable drinking spout appears. This behavior amounts to a second operant response which thus defines with the first response (i.e., wheel turning) an operant chain. In addition, once rats inserted and maintained their head in the magazine, the drinking spout was not continuously available but came “back and forth in the magazine during 50s.” This is a rather unusual method of fluid delivery (note: the frequency and duration of these back-and-forth movements are not indicated in the Methods).

Thus, to repeat, everything was made in the present paper to make access to sweet water reinforcement more difficult and less direct than access to cocaine reinforcement, thereby biasing choice towards cocaine. This unusual approach may be appropriate for addressing some scientific questions but it is misguided and inappropriate for studying the vulnerability to cocaine addiction which was the main goal of the present paper. If one wants to pursue such a goal, one better tries to make access to cocaine reinforcement equal to or more difficult than access to the nondrug option and not the other way around! Indeed, if one sufficiently weakens the nondrug option, then one will eventually reach a point where most individual rats, even the non-addicted ones, will prefer the drug! To take an extreme example, if one provides rats with ready access to cocaine but ask them to play piano or climb Mt Everest to get access to sweet water, they will surely choose cocaine over sweet water. This is not surprising, this is just trivial! In contrast, if rats take cocaine despite and at the expense of an equally or a more accessible potent nondrug option, then one has got something much less trivial and probably more relevant for studying the vulnerability to cocaine addiction.

On 2014 Aug 22, Serge Ahmed commented:

This study is interesting and also quite embarrassing. It is interesting because of the important questions that it asks. It is embarrassing because it shows that when given a choice, most rats prefer cocaine over sweet water – a finding that is strictly the opposite of what we and others have found over the past few years. Of course, contradiction and refutation are the “game of science”. We should not be embarrassed by them and instead welcome them.

My embarrassment comes from the fact that these opposite outcomes were obtained by a former master student of mine – Nathalie Vanhille who is the first author of this study – using a choice protocol initially developed in our lab. When Nathalie was working in our lab using this protocol, she observed that most rats preferred sweet water over cocaine – the opposite of what she now reports in this study despite the use of an identical choice protocol.

But were the choice protocols really identical? Of course not! Like always, the devil lurks into the details and details can sometimes matter a lot! Apparently, this study differs from our previous choice studies in the way rats were given access to sweet water. In our study, access to sweet water was pretty straightforward. Rats had to press a lever to fill a nearby receptacle with sweet water. Then they could obtain additional volumes of sweet water during 20s by continually licking the receptacle. In this study, however, access to sweet water was really contrived for reasons that remain unclear until one reaches the middle of the Discussion. In fact, despite my best efforts and those of other members of the team, we were unable to get a clear final picture of how rats get access to sweet water in this study.

So here is my challenge for the interested readers and researchers: I would really appreciate if someone could help me figure out how exactly rats get access to sweet water in this study.

Thank you!

On 2014 Aug 22, Serge Ahmed commented:

This study is interesting and also quite embarrassing. It is interesting because of the important questions that it asks. It is embarrassing because it shows that when given a choice, most rats prefer cocaine over sweet water – a finding that is strictly the opposite of what we and others have found over the past few years. Of course, contradiction and refutation are the “game of science”. We should not be embarrassed by them and instead welcome them.

My embarrassment comes from the fact that these opposite outcomes were obtained by a former master student of mine – Nathalie Vanhille who is the first author of this study – using a choice protocol initially developed in our lab. When Nathalie was working in our lab using this protocol, she observed that most rats preferred sweet water over cocaine – the opposite of what she now reports in this study despite the use of an identical choice protocol.

But were the choice protocols really identical? Of course not! Like always, the devil lurks into the details and details can sometimes matter a lot! Apparently, this study differs from our previous choice studies in the way rats were given access to sweet water. In our study, access to sweet water was pretty straightforward. Rats had to press a lever to fill a nearby receptacle with sweet water. Then they could obtain additional volumes of sweet water during 20s by continually licking the receptacle. In this study, however, access to sweet water was really contrived for reasons that remain unclear until one reaches the middle of the Discussion. In fact, despite my best efforts and those of other members of the team, we were unable to get a clear final picture of how rats get access to sweet water in this study.

So here is my challenge for the interested readers and researchers: I would really appreciate if someone could help me figure out how exactly rats get access to sweet water in this study.

Thank you!

On 2014 Nov 11, Serge Ahmed commented:

This comment is a follow-up of my previous comment about the difficulty in interpreting this study that contradicts most previous similar studies. After a careful analysis of this paper and after collecting all elements of methods “ectopically scattered” through the text, I think I finally arrived at a satisfactory explanation for why most rats preferred cocaine over sweet water in the present study. Briefly, everything was made to make access to sweet water reinforcement less direct and more difficult than access to cocaine reinforcement, thereby biasing choice towards cocaine!

More specifically, rats had to go through an unusually long chain of behavioral events before getting access to sweet water. A similar chain was not required for cocaine delivery. First, once rats turned the wheel on the operant panel, they had to cross the cage to reach a magazine on the opposite panel inside which there was a retractable drinking spout that delivered sweet water. This arrangement introduces a spatial and thus a time gap between responding and sweet water reinforcement. Both gaps are known to reduce conditioning. Second, once rats have reached the magazine, they did not have directly access to the drinking spout that delivered sweet water. They had first to insert their head into the magazine to make the retractable drinking spout appears. This behavior amounts to a second operant response which thus defines with the first response (i.e., wheel turning) an operant chain. In addition, once rats inserted and maintained their head in the magazine, the drinking spout was not continuously available but came “back and forth in the magazine during 50s.” This is a rather unusual method of fluid delivery (note: the frequency and duration of these back-and-forth movements are not indicated in the Methods).

Thus, to repeat, everything was made in the present paper to make access to sweet water reinforcement more difficult and less direct than access to cocaine reinforcement, thereby biasing choice towards cocaine. This unusual approach may be appropriate for addressing some scientific questions but it is misguided and inappropriate for studying the vulnerability to cocaine addiction which was the main goal of the present paper. If one wants to pursue such a goal, one better tries to make access to cocaine reinforcement equal to or more difficult than access to the nondrug option and not the other way around! Indeed, if one sufficiently weakens the nondrug option, then one will eventually reach a point where most individual rats, even the non-addicted ones, will prefer the drug! To take an extreme example, if one provides rats with ready access to cocaine but ask them to play piano or climb Mt Everest to get access to sweet water, they will surely choose cocaine over sweet water. This is not surprising, this is just trivial! In contrast, if rats take cocaine despite and at the expense of an equally or a more accessible potent nondrug option, then one has got something much less trivial and probably more relevant for studying the vulnerability to cocaine addiction.