The Role of GABAB Receptors in Morphine Self-Administration

Abstract

Background: There is only little information about the effects of GABA receptors agonist and antagonist on morphine self-administration. Present study was designed to assess role of GABAB receptors in the regulation of morphine-reinforced self-administration.

Methods: THIS STUDY WAS PERFORMED IN FOUR GROUPS OF RATS: (1) Saline group, which received saline in the self-administration session. (2) Morphine group, which received morphine in saline solution in the self-administration session. (3) Baclofen + Morphine group, which received both baclofen 20 min before self- administration test and morphine in the self-administration session. (4) Phaclofen + Morphine group, which received both phaclofen 20 min before self- administration test and morphine in the self-administration session. The number of lever pressing and self-infusion were recorded.

Results: Morphine significantly increased the number of active lever pressing dose dependently in self-administration session in comparative with saline group. Administration of baclofen, 20 min before morphine self-administration produced significant decrease in the initiation of morphine self-administration during all session. Conversely, pre-treatment of phaclofen increased the number of active lever pressing and self-infusion in this test.

Conclusion: Our results indicated a short-term treatment by baclofen, reduced morphine-maintenance response in a dose-dependent manner, suggesting that GABAB receptor agonists could be useful for reversing the neuroadaptations related to opiates.

Keywords: Baclofen; morphine addiction; phaclofen; self-administration.

Figure 1

Comparison numbers of self-infusion (SI) between two groups of control and morphine. Rats received saline (control group) and morphine (morphine group) in self-administration apparatus. Saline 5 μL injected (icv) before each session and number of SI was compared among 2 groups using one-way ANOVA and student's t-test. Data are presented as mean ± SEM. There was significant difference between control and morphine groups. The number of SI in morphine group increased significantly except first 5 days (^*P< 0.05)

Figure 2

The number of self- infusion (SI) comparison between morphine, (BAC + M) and (PHA + M) groups. In three groups rats received morphine in self-administration apparatus and saline (morphine group), baclofen (BAC + M group) and phaclofen (PHA + M group) injected (icv) 20 min before each session and number of SI was compared among three groups using one-way ANOVA and student's t-test. Data are presented as mean ± SEM. This figure shows that pre-treatment with baclofen (GABAB receptors agonist) (100 nmol icv), decreased significantly SI in rats and pre-treatment with phaclofen (GABAB receptors antagonist) (100 nmol icv) increased significantly SI in comparative with morphine group in during 5-10 days (^*P < 0.05) (⁺P < 0.05)

Figure 3

Comparison number of reinforcement lever pressing and non-reinforcement lever pressing between saline and morphine groups during morphine self-administration. In the day testing rats received saline (saline and morphine groups) in self-administration apparatus and saline 5 μL injected (icv) 20 min before each session and number of RL and NRL was compared among 2 groups using one-way ANOVA and student's t-test. Data are presented as mean ± SEM. This figure shows that number of RL increased significantly in morphine group during 5-10 days. No significantly difference in the NRL was observed between two groups (^*P< 0.05)

Figure 4

Comparison number of reinforcement lever pressing and non-reinforcement lever pressing between morphine, (BAC + M) and (PHA + M) groups. In three groups rats received morphine in self-administration apparatus. And saline (morphine group), baclofen (BAC + M) groups and phaclofen (PHA + M) groups injected (icv), 20 min before each session. The number of RL and NRL was compared among three groups using one-way ANOVA and student's t-test. Data are presented as mean ± SEM. This figure shows that number of RL in (BAC + M) group decreased and in (PHA + M) group increased significantly during 5-10 days in comparative with morphine group (^*P< 0.05), (⁺P< 0.05). No significantly difference in the NRL was observed between three groups