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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

Apparatus and experimental protocol.The locomotor apparatus (A) consists of a rotating actuator anchored to a U-shaped bracket over a steel bowl-shaped arena (Med Associates; 18 in top diameter, 6 in bottom diameter, 6 in depth) containing a layer of Sani-chip bedding. The rat is attached to the actuator via 45 cm spring leash terminated with an alligator clip, which is hooked onto a cable tie around the neck for the duration of the test session. The apparatus registers rotational movements as the rat causes the actuator to pivot, accumulated by computer as quarter turns. The experimental procedure (B) consisted of three days of acclimation sessions in the locomotor arenas, followed by five injections of METH (1.0 mg/kg, i.p.) or saline separated by 48 hr (Days 1, 3, 5, 7 and 9). After each injection, rats were placed into the locomotor arenas for 90 min and their rotational data were recorded as quarter turns. Rats underwent locomotor testing following a saline injection on Day 15, and these data were balanced between groups assigned to mGluR5 treatment or vehicle treatment. On Day 16, the rats were given an injection of the mGluR5 ligand (CDPPB or fenobam) or vehicle, and tested 30 min later following a probe injection of METH (0.5 mg/kg, i.p.).
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f1: Apparatus and experimental protocol.The locomotor apparatus (A) consists of a rotating actuator anchored to a U-shaped bracket over a steel bowl-shaped arena (Med Associates; 18 in top diameter, 6 in bottom diameter, 6 in depth) containing a layer of Sani-chip bedding. The rat is attached to the actuator via 45 cm spring leash terminated with an alligator clip, which is hooked onto a cable tie around the neck for the duration of the test session. The apparatus registers rotational movements as the rat causes the actuator to pivot, accumulated by computer as quarter turns. The experimental procedure (B) consisted of three days of acclimation sessions in the locomotor arenas, followed by five injections of METH (1.0 mg/kg, i.p.) or saline separated by 48 hr (Days 1, 3, 5, 7 and 9). After each injection, rats were placed into the locomotor arenas for 90 min and their rotational data were recorded as quarter turns. Rats underwent locomotor testing following a saline injection on Day 15, and these data were balanced between groups assigned to mGluR5 treatment or vehicle treatment. On Day 16, the rats were given an injection of the mGluR5 ligand (CDPPB or fenobam) or vehicle, and tested 30 min later following a probe injection of METH (0.5 mg/kg, i.p.).

Mentions: Locomotor activity was assessed in a Rotorat System apparatus (Med Associates, Mt. St Albans, VT) that measured rotational ambulation, quantified as quarter turns in both directions, within a bowl-shaped arena (Figure 1A). The rats (N=43 in the CDPPB experiment,N=45 in the fenobam experiment) were divided into groups where half of the rats received five injections of 1 mg/kg METH dissolved in saline (1 ml/kg, i.p.), separated by 48 hours, and the other half received injections of saline of matching volume (Figure 1B). Each injection was immediately followed by a 90 min locomotor test session. After a 6-day waiting period in the colony room, all rats were given a saline injection (1 ml/kg, i.p.) and subjected to a locomotor test session. The next day, rats were injected with 0 (N=7), 30 (N=8) or 60 mg/kg (N=6–7) CDPPB in one experiment; or 0 (N=8), 10 (N=8) or 30 mg/kg (N=6–7) fenobam in the other experiment, and 30 min later given a challenge dose of 0.5 mg/kg METH and subjected to a 90 min locomotor test session.


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)

Apparatus and experimental protocol.The locomotor apparatus (A) consists of a rotating actuator anchored to a U-shaped bracket over a steel bowl-shaped arena (Med Associates; 18 in top diameter, 6 in bottom diameter, 6 in depth) containing a layer of Sani-chip bedding. The rat is attached to the actuator via 45 cm spring leash terminated with an alligator clip, which is hooked onto a cable tie around the neck for the duration of the test session. The apparatus registers rotational movements as the rat causes the actuator to pivot, accumulated by computer as quarter turns. The experimental procedure (B) consisted of three days of acclimation sessions in the locomotor arenas, followed by five injections of METH (1.0 mg/kg, i.p.) or saline separated by 48 hr (Days 1, 3, 5, 7 and 9). After each injection, rats were placed into the locomotor arenas for 90 min and their rotational data were recorded as quarter turns. Rats underwent locomotor testing following a saline injection on Day 15, and these data were balanced between groups assigned to mGluR5 treatment or vehicle treatment. On Day 16, the rats were given an injection of the mGluR5 ligand (CDPPB or fenobam) or vehicle, and tested 30 min later following a probe injection of METH (0.5 mg/kg, i.p.).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Apparatus and experimental protocol.The locomotor apparatus (A) consists of a rotating actuator anchored to a U-shaped bracket over a steel bowl-shaped arena (Med Associates; 18 in top diameter, 6 in bottom diameter, 6 in depth) containing a layer of Sani-chip bedding. The rat is attached to the actuator via 45 cm spring leash terminated with an alligator clip, which is hooked onto a cable tie around the neck for the duration of the test session. The apparatus registers rotational movements as the rat causes the actuator to pivot, accumulated by computer as quarter turns. The experimental procedure (B) consisted of three days of acclimation sessions in the locomotor arenas, followed by five injections of METH (1.0 mg/kg, i.p.) or saline separated by 48 hr (Days 1, 3, 5, 7 and 9). After each injection, rats were placed into the locomotor arenas for 90 min and their rotational data were recorded as quarter turns. Rats underwent locomotor testing following a saline injection on Day 15, and these data were balanced between groups assigned to mGluR5 treatment or vehicle treatment. On Day 16, the rats were given an injection of the mGluR5 ligand (CDPPB or fenobam) or vehicle, and tested 30 min later following a probe injection of METH (0.5 mg/kg, i.p.).
Mentions: Locomotor activity was assessed in a Rotorat System apparatus (Med Associates, Mt. St Albans, VT) that measured rotational ambulation, quantified as quarter turns in both directions, within a bowl-shaped arena (Figure 1A). The rats (N=43 in the CDPPB experiment,N=45 in the fenobam experiment) were divided into groups where half of the rats received five injections of 1 mg/kg METH dissolved in saline (1 ml/kg, i.p.), separated by 48 hours, and the other half received injections of saline of matching volume (Figure 1B). Each injection was immediately followed by a 90 min locomotor test session. After a 6-day waiting period in the colony room, all rats were given a saline injection (1 ml/kg, i.p.) and subjected to a locomotor test session. The next day, rats were injected with 0 (N=7), 30 (N=8) or 60 mg/kg (N=6–7) CDPPB in one experiment; or 0 (N=8), 10 (N=8) or 30 mg/kg (N=6–7) fenobam in the other experiment, and 30 min later given a challenge dose of 0.5 mg/kg METH and subjected to a 90 min locomotor test session.

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