Biomedical subjects

Kristen A Slanina

Publications and source records attributed to Kristen A Slanina.

3 recordsLinked to original sources

PubMed2005

Inhibition of cyclooxygenase-2 elicits a CB1-mediated decrease of excitatory transmission in rat CA1 hippocampus.

Cannabinoid receptor (CB1) ligands decrease excitatory and inhibitory transmission in the hippocampus, but the influence of endogenously formed cannabinoids (eCBs) on basal excitatory transmission remains uncertain. Here, we investigated the influence of eCBs on synaptic transmission in CA1 hippocampus using the slice preparation. Blockade of CB1 with the selective receptor antagonists SR141716 (rimonabant) or AM251 augmented synaptic responses evoked upon stimulation of the Schaffer collaterals. This effect persisted in the presence of bicuculline or CGP55845 to block GABA(A) or GABA(B) receptors, revealing a tonic eCB influence on excitatory transmission. Selective inhibition of cyclooxygenase-2 (COX-2) with meloxicam or NS-398 decreased excitatory responses partly in a CB1-dependent manner, independently of GABA(A) transmission. Paired-pulse paradigms suggested a presynaptic CB1 mechanism to decrease glutamate release. Inhibition of COX-1 or other routes of eCB degradation did not affect synaptic transmission. We conclude that COX-2 regulates the formation of CB1 ligands that decrease hippocampal excitatory transmission.

Animals↗

PubMed2005

Endocannabinoids restrict hippocampal long-term potentiation via CB1.

Cannabinoid ligands alter cognition and prevent long-term potentiation (LTP) of synaptic transmission, but the influence of endogenously formed cannabinoids (eCBs) on hippocampal LTP remains ambiguous. In the accompanying study, we showed that eCB levels regulated by cyclooxygenase-2 (COX-2) tonically decrease basal excitatory transmission. Here, we investigated the influence of eCBs on LTP in CA1 hippocampus. LTP elicited by moderate stimulations (20 or 50 pulses) was facilitated in slices treated with a CB1 antagonist, whereas LTP elicited with robust stimulations (100 or 200 pulses) was unchanged by CB1 blockade. LTP elicited with theta-burst stimulations also was facilitated with CB1 blockade, revealing a tonic inhibitory influence of eCBs on LTP induction. Conversely, inhibition of COX-2 prevented LTP elicited with theta burst stimulations. Inhibition of COX-1 or other routes of eCB degradation did not affect LTP. We conclude that COX-2 regulates the formation of CB1 ligands that negatively regulate LTP.

Animals↗

PubMed2004

Mice lacking 5-HT receptors show specific impairments in contextual learning.

Using 5-HT(7) receptor knockout mice it has been shown that the 5-HT(7) receptor is the main mediator of serotonin-induced hypothermia but very little is known about the relevance of 5-HT(7) receptors in behaviour. We here report that lack of 5-HT(7) receptors leads to a specific learning deficit that is not due to general sensory or behavioural deficits. The knockout mice show impaired contextual fear conditioning but no significant deficits in motor and spatial learning or cued and operant conditioning. In addition, we demonstrate that 5-HT(7) receptor knockout mice display decreased long-term synaptic plasticity within the CA1 region of the hippocampus. The results indicate an important role for the 5-HT(7) receptor in contextual hippocampal-dependent learning and suggest a possible neuronal correlate for such a role is present within the CA1 region of the hippocampus.

Adaptation, Ocular↗