Source Paper
Enhancement of Locomotor Activity and Conditioned Reward to Cocaine by Brain-Derived Neurotrophic Factor
Brian A. Horger, Christiana A. Iyasere, Melissa T. Berhow, Chad J. Messer, Eric J. Nestler et al.
Journal of Neuroscience • 1999
Cocaine Locomotor Activity with BDNF Infusion
Objective: To investigate the effect of brain-derived neurotrophic factor (BDNF) on stimulant-induced locomotor sensitization and psychomotor stimulant effects of cocaine on locomotor activity
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Equipment3
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Protocol Steps
Surgical implantation of minipumps
Chronically implanted minipumps were surgically placed to deliver BDNF into the nucleus accumbens or ventral tegmental area
Note: Minipumps delivered BDNF at 1-2.5 μg/d
View evidence from paper
“BDNF was infused into the nucleus accumbens (NAc) or ventral tegmental area over 2 weeks via chronically implanted minipumps (1–2.5 μg/d)”
BDNF infusion period
BDNF was continuously infused via minipumps into target brain regions
Note: Infusion occurred over 2 weeks prior to behavioral testing
View evidence from paper
“BDNF was infused into the nucleus accumbens (NAc) or ventral tegmental area over 2 weeks via chronically implanted minipumps”
Cocaine administration and locomotor activity measurement (Experiment 1)
Cocaine was administered intraperitoneally at doses of 5-15 mg/kg to BDNF-treated and control animals, and psychomotor stimulant effects on locomotor activity were measured
Note: BDNF enhanced initial stimulant effects and facilitated development of sensitization to repeated cocaine doses
View evidence from paper
“the psychomotor stimulant effects of cocaine (5–15 mg/kg, i.p.) were studied. We found that BDNF enhanced the initial stimulant effects of cocaine and seemed to facilitate the development of sensitization”
Conditioned reward testing with saline (Experiment 2)
Saline was administered and responding for conditioned reinforcers (CR) was measured on lever presses in BDNF-treated and control animals
Note: BDNF-treated rats showed twice as many CR responses compared with controls
View evidence from paper
“BDNF-treated rats showed twice as many CR responses compared with controls when saline was first administered”
Conditioned reward testing with cocaine (Experiment 2)
Cocaine (10 mg/kg, i.p.) was administered and responding for conditioned reinforcers was measured
Note: BDNF enhanced CR responding more than four times compared to control animals
View evidence from paper
“BDNF enhanced responding on the CR lever more than four times that seen in control animals after a cocaine injection (10 mg/kg, i.p.)”
Long-term follow-up testing
Behavioral testing continued for more than a month after BDNF infusions had stopped to assess persistence of effects
Note: Enhanced response to cocaine in BDNF-treated animals persisted, indicating long-lasting changes in mesolimbic dopamine system
View evidence from paper
“The enhanced response to cocaine in BDNF-treated animals persisted for more than a month after the BDNF infusions had stopped”
Locomotor sensitization testing in BDNF knock-out mice (Experiment 3)
Locomotor sensitization to cocaine was examined in heterozygous BDNF knock-out mice compared with wild-type littermates
Note: Development of sensitization was delayed in BDNF knock-out mice compared with wild-type littermates
View evidence from paper
“we examined locomotor sensitization to cocaine in heterozygous BDNF knock-out mice and found that the development of sensitization was delayed compared with wild-type littermates”