A Modified Two-Way Active Avoidance Test for Combined Contextual and Auditory Instrumental Conditioning

Available two-way active avoidance paradigms do not provide contextual testing, likely due to challenges in performing repetitive trials of context exposure. To incorporate contextual conditioning in the two-way shuttle box, we contextually modified one of the chambers of a standard two-chamber rat shuttle box with visual cues consisting of objects and black and white stripe patterns. During the 5 training days, electrical foot shocks were delivered every 10 s in the contextually modified chamber but were signaled by a tone in the plain chamber. Shuttling between chambers prevented an incoming foot shock (avoidance) or aborted an ongoing one (escape). During contextual retention testing, rats were allowed to freely roam in the box. During auditory retention testing, visual cues were removed, and tone-signaled shocks were delivered in both chambers. Avoidance gradually replaced escape or freezing behaviors reaching 80% on the last training day in both chambers. Rats spent twice more time in the plain chamber during contextual retention testing and had 90% avoidance rates during auditory retention testing. Our modified test successfully assesses both auditory and contextual two-way active avoidance. By efficiently expanding its array of outcomes, our novel test will complement standard two-way active avoidance in mechanistic studies and will improve its applications in translational research.

Effects of Pramipexole on Learning and Memory Processes in Naïve and Haloperidol-challenged Rats in Active Avoidance Test

Background: Parkinson’s disease (PD) is the second most common neurode-generative disease, usually detected by its motor symptoms. The non-motor symptoms, including cognitive deficits, have been of great interest to researchers in the last few decades. Aim: To assess the effect of pramipexole on learning and memory in naïve and haloperidol-challenged rats. Materials and methods: Male Wistar rats divided into 9 groups (n=8): naïve - saline, pramipexole 0.5; 1 and 3 mg/kg bw; Haloperidol groups - saline, haloperidol, haloperidol + pramipexole 0.5; 1 and 3 mg/kg bw. Two-way active avoidance test (TWAA) and activity cage were performed. The studied parameters were: number of conditioned and unconditioned responses, vertical and horizontal movements. Statistical analysis was done using SPSS 19. Results: The naïve experimental groups significantly increased the number of conditioned responses during the tests for short- and long-term memory, compared with the saline groups (p<0.05). During the short-memory test only the animals with the lowest dose of PMX significantly increased the number of unconditioned responses whereas during the long-term memory test all experimental groups increased the number of escapes in comparison with the saline groups (p<0.05). Challenge dose of haloperidol attenuates learning and memory in pramipexol treated rats. Only the highest dose of pramipexol showed significant increase in conditioned and unconditioned responses compared with the haloperidol group (p<0.05). Conclusion: Pramipexole improves learning and memory in naïve rats by enhancing dopaminergic neurotransmission. This is probably not the only mechanism involved. This is confirmed by the decrease in learning and memory ability in rats with haloperidol-challenge.

Effects of Long-Term Treatment with Atorvastatin and Rosuaastatin on Active Avoidance Test in Intact Rats

Summary Statins are widely used for treatment of hyperlipidemia. They have been shown to possess pleiotropic effects apart from their lipid-lowering activity - anti-inflammatory, immunomodulatory, and neuroprotective. Most studies suggest that statins can protect the brain against damage but it is not clear whether they improve cognitive function in patients without neuropathy. The aim of the present study was to investigate the effect of 3-month treatment with atorvastatin and rosuvastatin on learning and memory processes in rats without brain damage. Wistar rats were treated orally for 90 days with atorvastatin and rosuvastatin at a dose of 10 mg/kg b. w. in parallel with the vehicle-treated group. After that period, learning ability and memory retention was evaluated using an active avoidance test - automatic reflex conditioner (shuttle box). The learning session was carried out on 5 consecutive days. Memory retention test was performed on day 12. The following behavioral reactions were investigated: conditioned responses (avoidance), unconditioned responses (escapes), and intertrial crossings. We found increased number of conditioned responses in groups, treated with atorvastatin 10 mg/kg b.w., and with rosuvastatin 10 mg/kg b.w. during the learning session and on the memory retention test, as compared to the same-day control group. The atorvastatin-treated group showed an increased number of unconditioned responses on days 1 and 2, as compared to the control group. In the group treated with Rosuvastatin there was an increased number of escapes on days 1,2 and 4, as compared to the vehicle-treated group. Atorvastatin and rosuvastatin at a dose of 10 mg/kg b.w. improved processes of learning and memory retention after the 3-month treatment.

Effect of Atorvastatin and Rosuvastatin on Learning and Memory in Rats with Diazepam-Induced Amnesia

ABSTRACT During the past decade, evidence has emerged that statins have neuroprotective effects. AIM: The aim of this study was to investigate the effects of atorvastatin and rosuvastatin on learning and memory in rats with diazepam-induced amnesia. MATERIAL AND METHODS: Experiments were carried out on 48 white male Wistar rats, divided into 6 groups, each of 8 rats. The experimental animals were treated per os for 14 days with atorvastatin and rosuvastatin in doses of 10 mg/kg and 20 mg/kg body weight, respectively. To induce amnesia diazepam was administered intraperitoneally in a dose of 2.5 mg/kg bw. Cognitive skills of the animals were examined after the induction of amnesia with active avoidance test using autonomic reflex conditioner (shuttle box) and passive avoidance tests (step-through and step down) (Ugo Basile, Italy). The following parameters were assessed: number of conditioned responses (avoidances), number of unconditioned responses (escapes) and number of intertrial crossings in the active avoidance test; latency of reactions was measured in the passive avoidance tests. RESULTS: We found a significant increase of conditioned responses in atorvastatin treated animals (in a dose of 10 mg/kg bw) in active avoidance training. In the animals treated with rosuvastatin in both doses there was a statistically significant increase of unconditioned responses. In the step-through passive avoidance test there was significant improvement of short-term and long-term memory following administration of atorvastatin (10 mg/kg bw). Rosuvastatin (10 mg/kg bw) preserves long-term memory. In the step-down passive avoidance test, atorvastatin (10 mg/kg bw) and rosuvastatin (10 mg/kg bw and 20 mg/kg bw) preserve long-term memory. CONCLUSIONS: Atorvastatin (10 mg/kg bw) and rosuvastatin (10 mg/kg and 20 mg/kg bw) improve cognitive functions in rats with diazepam-induced amnesia and preserve longterm memory.