The Reinforcing Properties of Nicotine

Wren Dwinell Author

08/06/2021 Added

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A brief explanation of nicotine self-administration data in rats.

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[00:00:02.340]Hi,
[00:00:02.700]I'm Wren Dwinell and I'm a biological sciences major here at the university of
[00:00:06.480]Nebraska Lincoln.
[00:00:07.740]The objective of my summer research surrounds nicotine and its positive
[00:00:11.040]reinforcement properties.
[00:00:12.690]We seek to understand the prevalence of nicotine addiction,
[00:00:15.090]despite the relatively low reinforcement value compared to other drugs.
[00:00:18.780]Meaning nicotine doesn't have a strong high,
[00:00:20.670]but it's still an enjoyable and frequently repeated experience to users.
[00:00:24.570]We're looking to understand this phenomenon due to the high correlation of heart
[00:00:27.690]disease and various cancers to nicotine use understanding the mechanism or
[00:00:31.860]mechanisms behind nicotine and its effects on the brain may reveal how we can
[00:00:35.430]better treat nicotine addiction.
[00:00:38.670]Our testing used rat models.
[00:00:40.440]Fitted with jugular vein catheters,
[00:00:42.270]which allowed us to hook the subjects up to IVs.
[00:00:45.660]After recovery from the implant of their catheters,
[00:00:48.030]rats were assigned to a paired or unpaired group during testing sessions,
[00:00:52.470]both the paired and unpaired groups received an infusion of nicotine 10 times
[00:00:56.580]within a two hour period.
[00:00:58.290]The paired group received access to sucrose in the 30 seconds,
[00:01:01.350]following their infusion of nicotine and the unpaired group received access to
[00:01:04.830]sucrose and a four to six minutes following each infusion.
[00:01:09.720]These are the results of the conditioning phase shown here.
[00:01:12.450]The four differeny concentrations of the nicotine doses.
[00:01:14.730]Given there's a general trend showing that the lower the nicotine dose,
[00:01:18.180]the lower the correlation between nicotine and the positive stimulus of sucrose
[00:01:21.810]learned during the conditioning phase,
[00:01:24.180]the difference score refers to the number of entries to the sucrose delivering
[00:01:27.780]mechanism during the 30 seconds,
[00:01:29.520]following a nicotine infusion versus the 30 seconds preceding the infusion.
[00:01:34.710]So keep in mind that for the paired group,
[00:01:36.450]they received sucrose 30 seconds following the infusions while the unpaired group
[00:01:40.680]does not.
[00:01:41.730]So the results here show that with the 0.03 and the 0.01 doses for the paired
[00:01:46.020]group,
[00:01:46.680]the subjects were able to associate the nicotine infusions with the receival
[00:01:50.370]of sucrose.
[00:01:51.600]While for the 0.003 and saline doses,
[00:01:55.500]there was no significant association learned and for the unpaired groups as
[00:01:59.580]well,
[00:01:59.790]there was no association as the sucrose retrieval and the nicotine infusions are
[00:02:03.780]set too far apart to create any correlation which is significant with, or,
[00:02:08.880]consistent rather with our hypothesis for these groups,
[00:02:15.220]this slide follows the same four dose concentrations through the next phase of
[00:02:18.960]the experiment where the subjects are allowed to self administer nicotine using
[00:02:22.590]nosepoke mechanisms, as shown by the graphs,
[00:02:26.910]the two highest concentrations of nicotine after conditioning insight,
[00:02:30.660]the most self administrations of nicotine.
[00:02:33.150]Another important note is that this phase is on a progressive ratio schedule,
[00:02:37.710]meaning that each subsequent infusion requires more nose pokes than the previous
[00:02:41.670]one to receive that infusion.
[00:02:44.580]The graphs indicate that the paired groups for the 0.03 and 0.01 concentration.
[00:02:49.320]show significant amounts of self-administration as well as the unpaired
[00:02:53.250]group for the 0.03, concentration.
[00:02:56.670]These results highlight for the 0.03 and 0.01 concentrations,
[00:03:00.670]the pair group consistently self administered frequently.
[00:03:03.820]What's most important to recognize about this data though,
[00:03:06.280]is that in those paired unpaired groups.
[00:03:11.320]Those in the unpaired groups are self-administering significantly less.
[00:03:15.010]So what this means is that the learning history with those paired groups makes a
[00:03:19.090]significant difference in the abuse liability of a drug.
[00:03:24.280]And as you can see,
[00:03:25.240]this graph is split into the male and female subjects and represents the total
[00:03:29.110]infusions here. We see the same idea of reiterated that those doses,
[00:03:33.700]that we're not reinforcing on their own were significantly more reinforcing
[00:03:37.450]after that learning history,
[00:03:39.400]the 0.01 dose was no more reinforcing than saline without a learning history in
[00:03:43.810]either sex yet in the females, the amount of infusion,
[00:03:46.660]the amount of infusions essentially doubled in the context of learning history,
[00:03:53.880]scrap is even more astounding because it touches on something I briefly
[00:03:56.880]mentioned in the beginning of this presentation, that is,
[00:03:59.340]there are different mechanisms to which the males and females experience the
[00:04:02.850]effects of nicotine.
[00:04:04.320]So the left side of the graph suggests that females experience significantly
[00:04:07.590]more reinforcement from nicotine when it is paired with a learning history.
[00:04:11.310]And on the right side,
[00:04:12.060]we see a difference between the paired and unpaired groups,
[00:04:14.580]but that female side is much more dramatic in that respect from this,
[00:04:17.910]we can say that our findings are consistent with literature following nicotine's
[00:04:21.120]effects on humans,
[00:04:22.500]which state that men are more susceptible to the actual pharmacological effects
[00:04:26.220]of nicotine while women are more susceptible to
[00:04:29.820]nicotine paired with environmental and other stimuli.
[00:04:34.230]So essentially the big takeaways are that rats can learn associations between
[00:04:38.340]nicotine and other external stimuli. In our example,
[00:04:41.130]sucrose and one set association is learned. It can create,
[00:04:45.220]it can increase abuse, liability, uh, which means that it takes doses,
[00:04:50.220]that weren't reinforcing without a history and make some reinforcing with that
[00:04:54.330]history,
[00:04:56.100]male and female subjects also experienced nicotine through different mechanisms
[00:05:00.030]that corresponded previous literature focused on humans.
[00:05:03.030]And finally learning history that conditioning of the paired versus unpaired
[00:05:06.570]groups makes a drastic difference in the abuse potential of nicotine.
[00:05:11.910]Also because of these findings,
[00:05:13.410]what we're we've currently been progressing with is pairing alcohol to nicotine
[00:05:17.040]due to the two commonly being used together in a human context,
[00:05:21.600]we don't currently have much good looking data with that right now,
[00:05:24.180]but it's something we're excited to keep moving forward with considering those
[00:05:27.570]interesting sex differences in those last graphs. So lastly,
[00:05:33.210]thank a few people who have been crucial to my work in the lab.
[00:05:36.720]So first our lab tech Sydney Houser, who trained me on the project.
[00:05:40.560]And of course, my PI Dr. Rick Bevins, who made the project possible,
[00:05:45.060]and also hired me on the project. And of course my advisor,
[00:05:49.560]Dr. Scott Barrett,
[00:05:50.880]who has encouraged me to get as involved with the project as possible.
[00:05:54.630]And thank you for listening to my talk.

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The Reinforcing Properties of Nicotine

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