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Effect of (S)-3,5-DHPG on learning, exploratory activity and anxiety in rats with experimental hypoxia
Agnieszka Nadlewska1, Halina Car, Robert Oksztel
1Department of Pharmacology, Medical Academy, Białystok, Poland.
Abstract:
We investigated the effects of (S)-3,5-DHPG, a selective agonist of group I metabotropic glutamate receptors (I mGluRs), on certain behaviors in rats after short-term hypoxia as a model of experimentally induced amnesia. The effect of (S)-3,5-DHPG administered intracerebroventriculary (icv) at doses of 0.01, 0.1 and 1.0 nmol was assessed using behavioral tests: the open field test, the passive avoidance response and the elevated "plus" maze test. (S)-3,5-DHPG did not change the number of crossed fields and rearings and only at a dose of 0.01 nmol it increased the number of bar approaches in the open field test. (S)-3,5-DHPG used at all doses improved consolidation, and at doses of 0.01 and 1.0 nmol it improved retrieval in the passive avoidance test. (S)-3,5-DHPG did not produce any significant effects in control rats in the elevated "plus" maze test. Hypoxia inhibited locomotor and exploratory activity of rats, significantly impaired consolidation and retrieval processes. We observed tendency to shortening the time spent in open arms and to decrease in the number of entries into open arms in the elevated "plus" maze in rats with underwent hypoxia. In hypoxia-treated groups of rats, (S)-3,5-DHPG inhibited locomotor and exploratory activity in comparison with the control groups administered (S)-3,5-DHPG. Hypoxia significantly inhibited beneficial effects of (S)-3,5-DHPG on consolidation and retrieval in passive avoidance. (S)-3,5-DHPG only at the dose of 1.0 nmol used before hypoxia improved consolidation and at the dose of 0.01 nmol enhanced retrieval in comparison with saline-treated group subjected to hypoxia. (S)-3,5-DHPG only at the dose of 1.0 nmol in hypoxia-treated group shortened the time spent in closed arms and increased the number of entries into closed and open arms in the elevated "plus" maze vs saline-treated group subjected to hypoxia. In rats subjected to hypoxia, (S)-3,5-DHPG, the agonist of I mGluRs, improved consolidation and retrieval and exhibited anxiolytic activity in dose-dependent manner.
Insights
Group I metabotropic glutamate receptor (I mGluR) agonist (S)-3,5-DHPG shows potential in improving memory and reducing anxiety in rats. However, its beneficial effects on memory consolidation and retrieval are significantly diminished by hypoxia.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Short-term hypoxia serves as an experimental model for induced amnesia.
- Group I metabotropic glutamate receptors (I mGluRs) play a role in cognitive functions.
Purpose of the Study:
- To investigate the effects of (S)-3,5-DHPG, a selective I mGluR agonist, on rat behavior following short-term hypoxia.
- To assess the impact of (S)-3,5-DHPG on memory consolidation, retrieval, and anxiety-like behaviors in a hypoxia-induced amnesia model.
Main Methods:
- Rats were subjected to short-term hypoxia to model amnesia.
- (S)-3,5-DHPG was administered intracerebroventricularly at varying doses (0.01, 0.1, 1.0 nmol).
- Behavioral tests included the open field test, passive avoidance response, and elevated plus maze test.
Main Results:
- (S)-3,5-DHPG improved memory consolidation and retrieval in the passive avoidance test, and exhibited anxiolytic activity in the elevated plus maze.
- Hypoxia impaired locomotor activity, memory consolidation, and retrieval.
- Hypoxia significantly reduced the beneficial effects of (S)-3,5-DHPG on memory, though some effects persisted at specific doses.
Conclusions:
- (S)-3,5-DHPG demonstrates therapeutic potential for memory deficits and anxiety.
- Hypoxia significantly counteracts the pro-cognitive and anxiolytic effects of (S)-3,5-DHPG, highlighting the vulnerability of these pathways to oxygen deprivation.