Intervention of the Gamma-Aminobutyric Acid Type B Receptors of the Amygdala Central Nucleus on the Sensitivity of the Morphine-Induced Conditionally Preferred Location in Wistar Female Rats

Abstract

Background: The amygdala is one of the nerve centers involved in drug reward. It is suggested that the central nucleus of the amygdala (CeA) is involved in morphine dependency. The CeA gamma-aminobutyric acid-ergic (GABAergic) system is a mediator of morphine rewarding effects. In this research, the effects of stimulation or inhibition of CeA GABA type B (GABAB) receptors on sensitization acquisition to morphine-induced reward was evaluated in Wistar female rats using conditioned place preferential (CPP) method.

Methods: Wistar female rats provided by Shahid Beheshti University, Tehran, Iran, were allocated into 17 groups including 7 groups of determining morphine dose-response, 2 groups of sensitivity and control, and 8 groups of different doses of agonists and antagonists in the acquisition stage (n = 7 in each group). Various quantities of morphine (0.5, 1, 2.5, 5, 7.5, 10 mg/kg of animal weight) were used to determine the effective and neutral doses of morphine. After 5 days from the start of the surgery, sensitization was induced. After the end of the sensitization period, CPP was conducted. Baclofen and CGP35348, as an agonist and antagonist of GABAB respectively, with the dose of 1.5, 6 and 12 μg/rat were inserted to the CeA, ten minutes before taking morphine.

Findings: Administration of baclofen had no significant effect on the acquisition of morphine sensitization. In contrast, injection of CGP35348 reduced the sensitivity to morphine.

Conclusion: GABA receptors can be effective in reducing morphine tendency by specific receptors, so these sites can be important therapeutic targets in counteracting the effects of drug abuse.

Keywords: Amygdala; Baclofen; Morphine; Rats.

Figure 1

Figure 1. Sensitization timeline SC: Subcutaneous; CPP: Conditioned place preferential

Figure 2

Figure 2. Conditioned place preferential (CPP) timeline for dose-response determination In the plan, only one dose of morphine is shown (0.5 mg/kg, SC), the rest of dosages (1, 2.5, 5, 7.5, 10 mg/kg) were likewise examined SC: Subcutaneous

Figure 3

Figure 3. Morphine dose-response in conditioned place preferential (CPP) paradigm (n = 7) Data are shown as mean ± standard error of the mean (SEM), *P < 0.001 for saline vs. 7.5 and saline vs. 10

Figure 4

Figure 4. Comparison of conditioned place preferential (CPP) in sensitized and control groups (n = 7) Data are shown as mean ± standard error of the mean (SEM), *P < 0.001

Figure 5

Figure 5. Effects of the intra-CeA administration of baclofen on the acquisition of conditioned place preferential (CPP) in morphine-induced sensitization (n = 7) Data are shown as mean ± standard error of the mean (SEM)

Figure 6

Figure 6. Effects of the intra-CeA administration of CGP35348 on the acquisition of conditioned place preferential (CPP) in morphine-induced sensitization (n = 7) Data are shown as mean ± standard error of the mean (SEM), *P < 0.05 for saline vs. other groups

Figure 7

Figure 7. Acquisition of sensitization to morphine timeline iCeA: Intra-CeA; SC: Subcutaneous; CPP: Conditioned place preferential