Related Experiment Videos
Cholinergic blockade impairs performance in operant DNMTP in two inbred strains of mice
Nuria Estapé1, Thomas Steckler
1Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, Munich D-80804, Germany.
Abstract:
Cholinergic blockade has been shown to impair performance in delayed nonmatching to position (DNMTP) paradigms in rats. In this study, a murine operant DNMTP task was used to assess the effects of cholinergic antagonism in two strains of mice (DBA/2 and C57BL/6) differing in spatial learning abilities. DNMTP was scheduled in operant chambers with retractable levers, where mice were trained until high levels of accuracy. Subsequently, proactive interference effects were assessed by manipulation of the intertrial interval (ITI), and animals were tested in this task under scopolamine (0.1-1.0 mg/kg) and mecamylamine (0.5-2.0 mg/kg) treatment. Data were analyzed according to the methods of signal detection theory. ITI manipulation decreased accuracy when the time between trials was reduced to 5 s. Cholinergic blockade failed to induce a pure mnemonic impairment but distinguishable effects of both receptor antagonists could be detected: scopolamine disrupted accuracy in a dose-dependent but delay-independent manner, whereas mecamylamine failed to impair accuracy, but decreased responsivity delay- and dose-dependently. Strains mainly differed in responsivity, with DBA/2 showing higher latencies to respond to the levers. These results are comparable to those obtained in rats. Thus, operant DNMTP can be applied to assess working memory in mice.
Insights
Cholinergic blockade impairs working memory in mice. Scopolamine reduced accuracy, while mecamylamine affected response times, indicating distinct effects on cognitive function in this delayed nonmatching to position task.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Cognitive Science
Background:
- Cholinergic systems are crucial for memory and learning.
- Previous studies in rats show cholinergic blockade impairs delayed nonmatching to position (DNMTP) performance.
- Two mouse strains, DBA/2 and C57BL/6, exhibit differential spatial learning abilities.
Purpose of the Study:
- To investigate the effects of cholinergic antagonism on working memory in mice using an operant DNMTP task.
- To compare the impact of scopolamine and mecamylamine on performance in two distinct mouse strains.
- To assess proactive interference by manipulating the intertrial interval (ITI).
Main Methods:
- An operant DNMTP task was employed with retractable levers in specialized chambers.
- Mice (DBA/2 and C57BL/6) were trained to high accuracy levels.
- Scopolamine and mecamylamine were administered at varying doses, and the ITI was manipulated to induce proactive interference.
- Data were analyzed using signal detection theory.
Main Results:
- Reducing the ITI to 5 seconds decreased accuracy, indicating proactive interference.
- Scopolamine impaired accuracy in a dose-dependent, delay-independent manner.
- Mecamylamine did not impair accuracy but decreased responsivity in a dose- and delay-dependent manner.
- DBA/2 mice showed longer latencies to respond compared to C57BL/6 mice.
Conclusions:
- Cholinergic blockade in mice does not cause a pure mnemonic impairment but affects different aspects of performance.
- The operant DNMTP task is a viable model for assessing working memory in mice.
- Distinct effects of muscarinic (scopolamine) and nicotinic (mecamylamine) antagonism highlight differential roles in cognitive processes.