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Positive or negative allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) does not alter expression of behavioral sensitization to methamphetamine.

Kufahl PR, Nemirovsky NE, Watterson LR, Zautra N, Olive MF - F1000Res (2013)

Bottom Line: The mGluR5 positive allosteric modulator (3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) and negative allosteric modulator fenobam were tested in separate experiments.Prior to the challenge test session, rats were injected with CDPPB, fenobam, or a vehicle.  Doses from previous studies showed reduced drug-conditioned behavior; however in this study neither CDPPB nor fenobam pretreatment resulted in an altered expression of behavioral sensitization, indicating a lack of mGluR5 involvement in sensitized methamphetamine-induced locomotion.Additionally, the high dose (30 mg/kg) of fenobam resulted in decreased methamphetamine-induced locomotion in rats regardless of drug exposure history, which suggests evidence of nonspecific behavioral inhibition.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, Arizona State University, Tempe, AZ, 85287-1104, USA.

ABSTRACT
We investigated the role of metabotropic glutamate receptor type 5 (mGluR5) in methamphetamine-induced behavioral sensitization. The mGluR5 positive allosteric modulator (3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) and negative allosteric modulator fenobam were tested in separate experiments. Sprague-Dawley rats were repeatedly injected with 1 mg/kg methamphetamine or saline, and then given a locomotor challenge test using a dose of 0.5 mg/kg methamphetamine. Prior to the challenge test session, rats were injected with CDPPB, fenobam, or a vehicle.  Doses from previous studies showed reduced drug-conditioned behavior; however in this study neither CDPPB nor fenobam pretreatment resulted in an altered expression of behavioral sensitization, indicating a lack of mGluR5 involvement in sensitized methamphetamine-induced locomotion. Additionally, the high dose (30 mg/kg) of fenobam resulted in decreased methamphetamine-induced locomotion in rats regardless of drug exposure history, which suggests evidence of nonspecific behavioral inhibition.

No MeSH data available.


Related in: MedlinePlus

Effects of mGluR5 treatment on baseline locomotion in previously drug-naïve rats.CDPPB (A) or fenobam (B) was injected 30 min prior to locomotor testing. No significant effects were reported from the quarter turns collected over 90 min sessions.
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f3: Effects of mGluR5 treatment on baseline locomotion in previously drug-naïve rats.CDPPB (A) or fenobam (B) was injected 30 min prior to locomotor testing. No significant effects were reported from the quarter turns collected over 90 min sessions.

Mentions: All of the tested doses of CDPPB and fenobam had negligible effects on baseline locomotion, measured 30 min after time of injection. Both the 60 mg/kg dose of CDPPB (300 ± 92 quarter turns, vs. 345 ± 43 for the vehicle) and the 30 mg/kg dose of fenobam (389 ± 59 quarter turns, vs. 407 ± 74 for the vehicle) produced slightly attenuated locomotor responses, but no significant effects were revealed by ANOVA in either experiment (Figure 3 andTable S9–Table S10).


Positive or negative allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) does not alter expression of behavioral sensitization to methamphetamine.

Kufahl PR, Nemirovsky NE, Watterson LR, Zautra N, Olive MF - F1000Res (2013)

Effects of mGluR5 treatment on baseline locomotion in previously drug-naïve rats.CDPPB (A) or fenobam (B) was injected 30 min prior to locomotor testing. No significant effects were reported from the quarter turns collected over 90 min sessions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814922&req=5

f3: Effects of mGluR5 treatment on baseline locomotion in previously drug-naïve rats.CDPPB (A) or fenobam (B) was injected 30 min prior to locomotor testing. No significant effects were reported from the quarter turns collected over 90 min sessions.
Mentions: All of the tested doses of CDPPB and fenobam had negligible effects on baseline locomotion, measured 30 min after time of injection. Both the 60 mg/kg dose of CDPPB (300 ± 92 quarter turns, vs. 345 ± 43 for the vehicle) and the 30 mg/kg dose of fenobam (389 ± 59 quarter turns, vs. 407 ± 74 for the vehicle) produced slightly attenuated locomotor responses, but no significant effects were revealed by ANOVA in either experiment (Figure 3 andTable S9–Table S10).

Bottom Line: The mGluR5 positive allosteric modulator (3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) and negative allosteric modulator fenobam were tested in separate experiments.Prior to the challenge test session, rats were injected with CDPPB, fenobam, or a vehicle.  Doses from previous studies showed reduced drug-conditioned behavior; however in this study neither CDPPB nor fenobam pretreatment resulted in an altered expression of behavioral sensitization, indicating a lack of mGluR5 involvement in sensitized methamphetamine-induced locomotion.Additionally, the high dose (30 mg/kg) of fenobam resulted in decreased methamphetamine-induced locomotion in rats regardless of drug exposure history, which suggests evidence of nonspecific behavioral inhibition.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, Arizona State University, Tempe, AZ, 85287-1104, USA.

ABSTRACT
We investigated the role of metabotropic glutamate receptor type 5 (mGluR5) in methamphetamine-induced behavioral sensitization. The mGluR5 positive allosteric modulator (3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) and negative allosteric modulator fenobam were tested in separate experiments. Sprague-Dawley rats were repeatedly injected with 1 mg/kg methamphetamine or saline, and then given a locomotor challenge test using a dose of 0.5 mg/kg methamphetamine. Prior to the challenge test session, rats were injected with CDPPB, fenobam, or a vehicle.  Doses from previous studies showed reduced drug-conditioned behavior; however in this study neither CDPPB nor fenobam pretreatment resulted in an altered expression of behavioral sensitization, indicating a lack of mGluR5 involvement in sensitized methamphetamine-induced locomotion. Additionally, the high dose (30 mg/kg) of fenobam resulted in decreased methamphetamine-induced locomotion in rats regardless of drug exposure history, which suggests evidence of nonspecific behavioral inhibition.

No MeSH data available.


Related in: MedlinePlus