Transcript Effects of early methylphenidate exposure on cannabinoid

Effects of early methylphenidate
exposure on cannabinoid-induced
conditioned place preference in
young adult male rats
Michelle J. Stone, Christopher P. Plant, Andrea D. Hardin,
Zachary R. Harmony, Cynthia A. Crawford
Background

Methylphenidate is commonly prescribed to treat
Attention Deficit Hyperactivity Disorder (ADHD) in late
childhood

Adults diagnosed of ADHD report higher level of cannabis
than adults who have not been diagnosed with ADHD


Cannabis is a psychoactive drug that binds with high affinity
to receptors in the endocannabinoid system
Research Question: Does early methylphenidate exposure
enhance the rewarding properties of cannabis in
adulthood?
The Current Study

The current study examined the preference for a
cannabinoid agonist in male Sprague Dawley adult
rats after they had been pretreated with
methylphenidate in early adolescence.

Specifically, we examined if early
methylphenidate exposure enhances the
rewarding properties of the cannabinoid agonist,
CP 55,940, utilizing the conditioned place
preference (CPP) paradigm.
Methods and Materials
Animals

81 Male Sprague Dawley rats

5-7 rats per group

Bred in the vivarium of the Psychology department at
California State University, San Bernardino

All procedures were conducted according to the National
Institutes of Health (NIH) Guide for the Care and Use of
Laboratory Animals, and approved by the Institutional
Animal Care and Use Committee at CSUSB.

Food and water ad libitum

12/12 hour light/dark cycle
Experimental Procedures

Pretreatment from PD 21-30
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Intraperitoneal injection

Twice daily 6-8 hours apart for 10 days

0, 0.5,2 or 5 mg/kg

Left undisturbed from PD 31 through PD 56

Habituation from PD 56-59
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Animals were transported in groups of 3-4 into the experiment
room

Handled for 10 minutes each day
Conditioned Place Preference

T-shaped chamber
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Two adjacent compartments (24x30x45)
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White with mesh flooring and pine bedding
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Black with bar flooring and cedar bedding
A choice compartment (24x10x45) allows entry into both larger
adjacent compartments
 Painted gray with solid floor
Drug treatment
Drugs were delivered every other day during conditioning in a
counterbalanced fashion
 Cannabinoid agonist—CP 55,940



0, 10, 20 or 30 ug/kg
Vehicle
Conditioned Place Preference
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Preconditioning (PD 60)
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Animal starts in the choice compartment
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15 minutes of free access to both compartments
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Priming injection given in home cage 30 minutes after rats were returned to the
vivarium
Conditioning (PD 62-71)

Drug was paired with the non-preferred compartment and saline with the preferred
compartment on alternating days.
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Rats received 5 daily 30 min pairings on each side
Testing (PD 73)
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Starts from choice compartment
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15 minutes free access to both sides
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No drug given
Statistical Design
Analysis of Variance

Does early methylphenidate exposure enhance the
rewarding properties of cannabis in adulthood?

4 X 4 between subjects design
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Independent variables

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Methylphenidate pre-treatment (0, 0.5, 2.0, 5.0 mg/kg)

CP 55, 940 treatment ( 0,10, 20, 30 ug/kg)
Dependent variable
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Preference score
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Time spent on drug paired side on test day subtracted from the time
spent in the non-preferred chamber on the precondition day
Time spent in the white compartment
Preference for a cannabinoid agonist
Methylphenidate and its interaction with
the cannabinoid agonist CP 55, 940
Discussion
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Methylphenidate increased the amount of time spent in
the white compartment the on preconditioning day
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Reduced anxiety

Preference for the CP 55,940 cannabinoid agonist was only
seen with the 20 micro-gram dose
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There was no interaction between pretreatment with
methylphenidate and the cannabinoid agonist
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Methylphenidate did not increase the rewarding effects of CP
55,940
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Clinical implications
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Future directions
A special thank you to..
 Diversity-promoting
Institutions Drug Abuse
Research Program (DIDARP)
 Dr.
Cynthia Crawford
 Christopher

Plant
Andrea Hardin
 Zachary
Harmony