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Glutamate receptors in the dorsal hippocampus mediate the acquisition, but not the expression, of conditioned place aversion induced by acute morphine withdrawal in rats.

Hou YY, Liu Y, Kang S, Yu C, Chi ZQ, Liu JG - Acta Pharmacol. Sin. (2009)

Bottom Line: Conditioned place aversion (CPA) induced by naloxone-precipitated morphine withdrawal were assessed.However, intra-DH microinjection of D-AP5 or NBQX after conditioning but before the testing session had no effect on the expression of CPA.Our results suggest that NMDA and AMPA receptors in the dorsal hippocampus are involved in the acquisition, but not in the expression, of the negative motivational components of acute morphine withdrawal in rats.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

ABSTRACT

Aim: To evaluate the role of glutamate receptors in the dorsal hippocampus (DH) in the motivational component of morphine withdrawal.

Methods: NMDA receptor antagonist D-AP5 (5 microg/0.5 microL per side) or AMPA receptor antagonist NBQX (2 microg/0.5 microL per side) was microinjected into DH of rats. Conditioned place aversion (CPA) induced by naloxone-precipitated morphine withdrawal were assessed.

Results: Preconditioning microinjection of D-AP5 or NBQX into the DH impaired the acquisition of CPA in acute morphine-dependent rats. However, intra-DH microinjection of D-AP5 or NBQX after conditioning but before the testing session had no effect on the expression of CPA.

Conclusion: Our results suggest that NMDA and AMPA receptors in the dorsal hippocampus are involved in the acquisition, but not in the expression, of the negative motivational components of acute morphine withdrawal in rats.

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Effects of intra-DH infusion of D-AP5 or NBQX on the expression of conditioned place aversion induced by naloxone-precipitated morphine withdrawal in morphine-treated rats. D-AP5 (5 μg/0.5 μL per side), NBQX (2 μg/0.5 μL per side) or vehicle (0.5 μL per side) was bilaterally microinfused into the dorsal hippocampus 20 min before the testing session. The columns show the time spent in the drug-paired compartment in the preconditioning (Pre) or testing (test) sessions (A) and the CPA score (B). Data are expressed as means±SEM. cP<0.01 compared with the corresponding preconditioning session (Student's t test).
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fig4: Effects of intra-DH infusion of D-AP5 or NBQX on the expression of conditioned place aversion induced by naloxone-precipitated morphine withdrawal in morphine-treated rats. D-AP5 (5 μg/0.5 μL per side), NBQX (2 μg/0.5 μL per side) or vehicle (0.5 μL per side) was bilaterally microinfused into the dorsal hippocampus 20 min before the testing session. The columns show the time spent in the drug-paired compartment in the preconditioning (Pre) or testing (test) sessions (A) and the CPA score (B). Data are expressed as means±SEM. cP<0.01 compared with the corresponding preconditioning session (Student's t test).

Mentions: Considerable evidence has shown that the dorsal hippocampus is involved in contextual memory retrieval in several Pavlovian conditioning tasks, such as fear conditioning and morphine-induced CPP22, 23, 24, 25. In the CPA testing session, re-exposure to the training context elicited retrieval of the morphine withdrawal memory and the negative motivation induced by the morphine withdrawal-paired environment was then expressed as aversion. To examine the effects of D-AP5 or NBQX on the expression of the negative motivational effect of morphine withdrawal, each of the drugs was bilaterally microinjected into the dorsal hippocampus 20 min before the testing session. Figure 4 indicates that the intra-DH injection of D-AP5 or NBQX did not induce a change in the expression of CPA in the morphine-treated rats. In the vehicle, D-AP5 or NBQX-injected groups, significant differences (P<0.01, Student's t test) were observed between the time spent in the drug-paired compartment during the testing session (202.8± 52.8 s, 212.5±74.0 s and 187.4±46.2 s, respectively) and the time spent during the preconditioning session (630.6±35.5 s, 583.9±46.8 s and 575.8±58.8 s, respectively), indicative of the formation of morphine-withdrawal induced CPA(Figure 4A). One-way ANOVA indicated no significant difference in CPA score among the groups (F(2, 18)=0.15; P>0.05) (Figure 4B).


Glutamate receptors in the dorsal hippocampus mediate the acquisition, but not the expression, of conditioned place aversion induced by acute morphine withdrawal in rats.

Hou YY, Liu Y, Kang S, Yu C, Chi ZQ, Liu JG - Acta Pharmacol. Sin. (2009)

Effects of intra-DH infusion of D-AP5 or NBQX on the expression of conditioned place aversion induced by naloxone-precipitated morphine withdrawal in morphine-treated rats. D-AP5 (5 μg/0.5 μL per side), NBQX (2 μg/0.5 μL per side) or vehicle (0.5 μL per side) was bilaterally microinfused into the dorsal hippocampus 20 min before the testing session. The columns show the time spent in the drug-paired compartment in the preconditioning (Pre) or testing (test) sessions (A) and the CPA score (B). Data are expressed as means±SEM. cP<0.01 compared with the corresponding preconditioning session (Student's t test).
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Related In: Results  -  Collection

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fig4: Effects of intra-DH infusion of D-AP5 or NBQX on the expression of conditioned place aversion induced by naloxone-precipitated morphine withdrawal in morphine-treated rats. D-AP5 (5 μg/0.5 μL per side), NBQX (2 μg/0.5 μL per side) or vehicle (0.5 μL per side) was bilaterally microinfused into the dorsal hippocampus 20 min before the testing session. The columns show the time spent in the drug-paired compartment in the preconditioning (Pre) or testing (test) sessions (A) and the CPA score (B). Data are expressed as means±SEM. cP<0.01 compared with the corresponding preconditioning session (Student's t test).
Mentions: Considerable evidence has shown that the dorsal hippocampus is involved in contextual memory retrieval in several Pavlovian conditioning tasks, such as fear conditioning and morphine-induced CPP22, 23, 24, 25. In the CPA testing session, re-exposure to the training context elicited retrieval of the morphine withdrawal memory and the negative motivation induced by the morphine withdrawal-paired environment was then expressed as aversion. To examine the effects of D-AP5 or NBQX on the expression of the negative motivational effect of morphine withdrawal, each of the drugs was bilaterally microinjected into the dorsal hippocampus 20 min before the testing session. Figure 4 indicates that the intra-DH injection of D-AP5 or NBQX did not induce a change in the expression of CPA in the morphine-treated rats. In the vehicle, D-AP5 or NBQX-injected groups, significant differences (P<0.01, Student's t test) were observed between the time spent in the drug-paired compartment during the testing session (202.8± 52.8 s, 212.5±74.0 s and 187.4±46.2 s, respectively) and the time spent during the preconditioning session (630.6±35.5 s, 583.9±46.8 s and 575.8±58.8 s, respectively), indicative of the formation of morphine-withdrawal induced CPA(Figure 4A). One-way ANOVA indicated no significant difference in CPA score among the groups (F(2, 18)=0.15; P>0.05) (Figure 4B).

Bottom Line: Conditioned place aversion (CPA) induced by naloxone-precipitated morphine withdrawal were assessed.However, intra-DH microinjection of D-AP5 or NBQX after conditioning but before the testing session had no effect on the expression of CPA.Our results suggest that NMDA and AMPA receptors in the dorsal hippocampus are involved in the acquisition, but not in the expression, of the negative motivational components of acute morphine withdrawal in rats.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

ABSTRACT

Aim: To evaluate the role of glutamate receptors in the dorsal hippocampus (DH) in the motivational component of morphine withdrawal.

Methods: NMDA receptor antagonist D-AP5 (5 microg/0.5 microL per side) or AMPA receptor antagonist NBQX (2 microg/0.5 microL per side) was microinjected into DH of rats. Conditioned place aversion (CPA) induced by naloxone-precipitated morphine withdrawal were assessed.

Results: Preconditioning microinjection of D-AP5 or NBQX into the DH impaired the acquisition of CPA in acute morphine-dependent rats. However, intra-DH microinjection of D-AP5 or NBQX after conditioning but before the testing session had no effect on the expression of CPA.

Conclusion: Our results suggest that NMDA and AMPA receptors in the dorsal hippocampus are involved in the acquisition, but not in the expression, of the negative motivational components of acute morphine withdrawal in rats.

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