Objective: Selective kappa opioid receptor (KOR) agonists were shown to produce a dose-dependent depression of brain-stimulation reward (BSR) in the rat intracranial self-stimulation (ICSS) tests. However, limited studies using mice produced less conclusive results. Here the effects of U50,488H were re-examined on BSR in mice with a larger cohort of animals.
Results: Forty C57BL/6J male mice were implanted with the electrodes in medial forebrain bundle. About a week after surgery, mice were subject to ICSS training. Only eighteen passed the two-phase procedures, at which point they readily spun the wheels to obtain reinforcing effect of BSR, and were used for the ICSS tests. Compared with saline (s.c.), U50,488H (2 mg/kg, s.c.) did not have effects on the BSR thresholds within 1 h post-treatment, while it decreased the maximum wheel-spinning rates in a time-dependent manner. In contrast, cocaine (5 mg/kg, s.c.) decreased the BSR thresholds time-dependently without affecting the maximum wheel-spinning rates in the same cohort of mice, demonstrating the validity of our mouse ICSS models. For comparison, U50,488H (2 mg/kg, s.c.) induced significant conditioned place aversion (CPA) in a different cohort of mice without surgeries. Thus, ICSS may not be an appropriate test for KOR agonist-induced aversion in mice.

Figure 1

Figure 2

Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
Loading...
Posted 12 Aug, 2020
On 06 Aug, 2020
On 06 Aug, 2020
On 31 Jul, 2020
Received 29 Jul, 2020
On 23 Jul, 2020
Invitations sent on 21 Jul, 2020
On 21 Jul, 2020
Received 21 Jul, 2020
On 20 Jul, 2020
On 19 Jul, 2020
On 19 Jul, 2020
On 12 Jul, 2020
Received 10 Jul, 2020
Received 18 Jun, 2020
On 15 Jun, 2020
On 12 Jun, 2020
On 01 Jun, 2020
Invitations sent on 01 Jun, 2020
On 26 May, 2020
On 26 May, 2020
Posted 12 Aug, 2020
On 06 Aug, 2020
On 06 Aug, 2020
On 31 Jul, 2020
Received 29 Jul, 2020
On 23 Jul, 2020
Invitations sent on 21 Jul, 2020
On 21 Jul, 2020
Received 21 Jul, 2020
On 20 Jul, 2020
On 19 Jul, 2020
On 19 Jul, 2020
On 12 Jul, 2020
Received 10 Jul, 2020
Received 18 Jun, 2020
On 15 Jun, 2020
On 12 Jun, 2020
On 01 Jun, 2020
Invitations sent on 01 Jun, 2020
On 26 May, 2020
On 26 May, 2020
Objective: Selective kappa opioid receptor (KOR) agonists were shown to produce a dose-dependent depression of brain-stimulation reward (BSR) in the rat intracranial self-stimulation (ICSS) tests. However, limited studies using mice produced less conclusive results. Here the effects of U50,488H were re-examined on BSR in mice with a larger cohort of animals.
Results: Forty C57BL/6J male mice were implanted with the electrodes in medial forebrain bundle. About a week after surgery, mice were subject to ICSS training. Only eighteen passed the two-phase procedures, at which point they readily spun the wheels to obtain reinforcing effect of BSR, and were used for the ICSS tests. Compared with saline (s.c.), U50,488H (2 mg/kg, s.c.) did not have effects on the BSR thresholds within 1 h post-treatment, while it decreased the maximum wheel-spinning rates in a time-dependent manner. In contrast, cocaine (5 mg/kg, s.c.) decreased the BSR thresholds time-dependently without affecting the maximum wheel-spinning rates in the same cohort of mice, demonstrating the validity of our mouse ICSS models. For comparison, U50,488H (2 mg/kg, s.c.) induced significant conditioned place aversion (CPA) in a different cohort of mice without surgeries. Thus, ICSS may not be an appropriate test for KOR agonist-induced aversion in mice.

Figure 1

Figure 2

Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
Loading...