Possible overlapping time frames of acquisition and consolidation phases in object memory processes: a pharmacological approach

Abstract

In previous studies, we have shown that acetylcholinesterase inhibitors and phosphodiesterase inhibitors (PDE-Is) are able to improve object memory by enhancing acquisition processes. On the other hand, only PDE-Is improve consolidation processes. Here we show that the cholinesterase inhibitor donepezil also improves memory performance when administered within 2 min after the acquisition trial. Likewise, both PDE5-I and PDE4-I reversed the scopolamine deficit model when administered within 2 min after the learning trial. PDE5-I was effective up to 45 min after the acquisition trial and PDE4-I was effective when administered between 3 and 5.5 h after the acquisition trial. Taken together, our study suggests that acetylcholine, cGMP, and cAMP are all involved in acquisition processes and that cGMP and cAMP are also involved in early and late consolidation processes, respectively. Most important, these pharmacological studies suggest that acquisition processes continue for some time after the learning trial where they share a short common time frame with early consolidation processes. Additional brain concentration measurements of the drugs suggest that these acquisition processes can continue up to 4-6 min after learning.

Figure 1.

Effects of donepezil treatment on discrimination performance in an object recognition task using a 1-h interval in combination with scopolamine (A) or a 24-h retention interval (B). Asterisks indicate a difference from scopolamine/vehicle-treated (A) or vehicle-treated (B) animals, least significant difference (LSD): (**) P < 0.01; (***) P < 0.001, plus signs indicate a difference from the saline/vehicle-treated animals, +++P < 0.001 and differences from zero are indicated with hashes, one-sample t-test, #P < 0.05; ##P < 0.01; ###P < 0.001.

Figure 2.

Effects of vardenafil treatment on discrimination performance in an object recognition task using a 1 h interval in combination with scopolamine (A): adapted from a previous study (Akkerman et al. 2015) or a 24-h retention interval (B). Asterisks indicate a difference from scopolamine/vehicle-treated (A) or vehicle-treated (B) animals, LSD, (*) P < 0.05; (**) P < 0.01; (***) P < 0.001, plus signs indicate a difference from the saline/vehicle-treated animals (A), LSD, ++ P < 0.01; +++ P < 0.001 and differences from zero are indicated with hashes, one-sample t-test, # P < 0.05; ## P < 0.01; ### P < 0.001.

Figure 3.

Effects of rolipram treatment on discrimination performance in an object recognition task using a 1-h interval in combination with scopolamine (A) or a 24-h retention interval (B). Asterisks indicate a difference from scopolamine/vehicle-treated (A) or vehicle-treated (B) animals, LSD, (*) P = 0.062; (*) P < 0.05; (***) P < 0.001, plus signs indicate a difference from the saline/vehicle-treated animals (A), LSD, ++ P < 0.01 and differences from zero are indicated with hashes, one-sample t-test, # P < 0.05; ## P < 0.01; ### P < 0.001.

Figure 4.

Effects of rolipram treatment on discrimination performance in an object recognition task using a 24-h retention interval. Asterisks indicate a difference from vehicle-treated animals, independent samples t-tests; (*) P < 0.05; (**) P < 0.01 and differences from zero are indicated with hashes, one-sample t-test, # P < 0.05; ## P < 0.01.