Effects of Methylphenidate in combination with Nicotine of Ethanol Self Administration

Elijah Grablin and Patrick white Author

07/28/2021 Added

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This project looked into the reward enhancement effects of methylphenidate in combination with nicotine on ethanol self administration

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[00:00:00.540]Hello everyone I'm Elijah Grablin.
[00:00:02.310]And my name is Patrick White and our UCARE project was on the effects of
[00:00:05.340]methylphenidate in combination with nicotine ethanol Self-administration.
[00:00:10.400]To start us off, I'm going to explain what nicotine is.
[00:00:13.550]So nicotine is a stimulant. That is the main psychoactive component in tobacco.
[00:00:18.860]Nicotine is highly addictive and is a substance that's easy to develop
[00:00:22.610]dependency on. Uh,
[00:00:24.620]it's very dangerous as it causes changes in brain chemistry. It is, uh,
[00:00:28.970]smoking is the number one cause of preventable death, uh,
[00:00:32.000]disease and disability in the United States.
[00:00:34.670]And currently 34.1 billion adults smoke.
[00:00:39.650]The reason we're looking at nicotine is we're using the reward enhancing effect
[00:00:43.880]of nicotine in our project. Uh,
[00:00:45.980]the reward enhancing effect is a well-researched phenomenon regarding the
[00:00:50.270]effect, uh, the well-researched, uh, reward enhancing effect,
[00:00:54.500]including reward function and locomotor activity within the study. Uh,
[00:00:59.030]nicotine is a primary reinforcer with a potential of enhancing, uh,
[00:01:03.530]re reinforcing non-nicotine stimuli,
[00:01:06.260]such as conditioned stimuli to learn through associative learning.
[00:01:10.730]So stimuli associated with nicotine being reinforced are things such as
[00:01:15.470]food consumption, relaxation, social interaction,
[00:01:19.880]and it amplifies these reinforcing effects of many different rewards.
[00:01:25.850]So we'll also be using methylphenidate in tandem with the nicotine.
[00:01:30.800]So method methylphenidate is a stimulant drug that is used in many cases to
[00:01:34.610]treat attention deficit, hyperactivity disorder, or ADHD,
[00:01:38.180]as well as narcolepsy methylphenidate acts on the central nervous system by
[00:01:42.860]blocking the dopamine uptake and androgenic neurons by blocking
[00:01:47.750]the dopamine transport proteins.
[00:01:51.620]So the purpose of this study has three aims aim. One is,
[00:01:55.460]does methylphenidate have an effect on ethanol reinforcement? The second aim is,
[00:02:00.290]does methylphenidate alter the reward enhancing effects of nicotine on ethanol
[00:02:04.490]reinforcement.
[00:02:05.390]And the final third aim is will the effects of methylphenidate and or
[00:02:09.920]nicotine on ethanol maintained behavior vary by sex.
[00:02:13.820]So in order to test these aims, uh,
[00:02:16.010]we first received the rats and gave them four days to acclimate and get used to
[00:02:20.570]the colony. We, they also had some time to get used to us. Um,
[00:02:25.940]they were placed inside a opera chamber where they learned to press for 12%
[00:02:30.020]sucrose. There were two levers inside the opera chamber, the act of lever,
[00:02:34.940]which when pressed once, uh, gave them sucrose and an inactive lever,
[00:02:39.530]which when pressed to did nothing,
[00:02:42.080]the next phase of the experiment was to get the rats, um,
[00:02:47.120]do drink for an increasing amount of, uh, ethanol.
[00:02:51.200]So they first started on a solution that was 12% sucrose and
[00:02:55.940]2% ethanol. They did that for three days.
[00:02:59.320]Then they did a solution that was 12% sucrose, 4% ethanol.
[00:03:03.820]And this increased by two, um,
[00:03:06.910]until they reached 12% sucrose and 12% ethanol where they pressed for that for
[00:03:11.200]seven days to get consistent responding. After those seven days were up,
[00:03:16.270]we decrease the amount of sucrose in the solution from 12 to eight
[00:03:21.250]to four to six to, two, um,
[00:03:24.260]until they were pressing for just straight 12% ethanol.
[00:03:29.740]Um,
[00:03:30.070]they pressed on for that solution for seven days to get consistent responding.
[00:03:35.290]Um, the next phase was the MPH testing,
[00:03:40.360]uh, for the first three days of this, uh, testing.
[00:03:43.990]We bumped them from a one response, a FR of one,
[00:03:47.860]so that meaning they only had to press once to a VR two.
[00:03:50.500]So they had to press on average of tool two times then a VR three,
[00:03:54.220]which is an average of three times, and then to a progressive ratio schedule,
[00:03:57.580]which means that the next reinforcer costs one more than the previous.
[00:04:01.690]So the first time they have to press once the second time, twice,
[00:04:05.110]so on and so forth. But before they replaced inside the operant chamber,
[00:04:08.950]15 minutes before they were given one of the three doses in red.
[00:04:12.460]So either saline one or three milligrams per kilogram, methylphenidate,
[00:04:16.540]and five minutes before being placed inside the operant chamber,
[00:04:20.590]they were given one of the six doses in gray.
[00:04:23.230]So either saline or a varying dose of nicotine. Um,
[00:04:28.390]so here we have the data for the MP, for the Methylphenidate testing,
[00:04:33.040]on the Y axis is the grams per kilogram, uh,
[00:04:37.030]ethanol consumption.
[00:04:38.050]So this is the amount of grams that they consume based on their body weight. Uh,
[00:04:42.340]this data does come with an assumption that when the rats were presented the
[00:04:45.910]dipper and went for it, that they drank the entire contents of the dipper cup,
[00:04:51.310]um, on the X-axis and the colors is the different nicotine doses.
[00:04:55.870]So you can see the Sally's like an orange, uh,
[00:04:58.330]the 0.025 is like a brown, so on and so forth.
[00:05:03.010]Um, you can kind of see that the, um,
[00:05:07.090]high dose of methylphenidate is decreasing the amount of ethanol they are
[00:05:11.440]drinking based on their body weight, uh,
[00:05:14.410]results that we see from this are nicotine is increasing consumption and around
[00:05:19.600]0.1 milligrams per kilogram,
[00:05:21.700]nicotine and methylphenidate is decreasing consumption at the high dose,
[00:05:25.360]which was the 3.0 milligrams per kilogram, methylphenidate,
[00:05:31.780]um, some conclusions and future directions.
[00:05:35.050]So conclusions we can draw from our data is methylphenidate is acting like
[00:05:38.650]bupropion or its common name Wellbutrin
[00:05:42.310]which is a nicotine cessation aid,
[00:05:44.260]which acts on the same neurotransmitter as methylphenidate and that's dopamine.
[00:05:49.270]And it's decreasing the amount of consumption of ethanol. Uh,
[00:05:52.900]the nicotine enhancement of, uh,
[00:05:56.200]ethanol self administration is consistent with previous research,
[00:06:00.410]future directions that we can take, um, for this, uh,
[00:06:04.490]for projects like these are, we can use other ADHD medications, so Adderall,
[00:06:08.330]Vyvanse, uh, et cetera.
[00:06:11.300]We can also use antagonists for the dopamine. Um,
[00:06:15.590]so we can see if blocking those, uh,
[00:06:18.350]receptors will change the amount of ethanol dose decreasing or they're
[00:06:22.790]consuming and then we would like to acknowledge Dr.
[00:06:27.140]Scott Barrett and Dr. Rick Bevins in their help creating the project.
[00:06:31.100]And we would also like to thank Clayton and Molly for their help in running the
[00:06:34.520]project. Thank you.

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Effects of Methylphenidate in combination with Nicotine of Ethanol Self Administration

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