Audiogenic seizures can be induced in DBA/2J mice following intense auditory stimulation. A number of neurotransmitters, including
5-hydroxytryptamine (5-HT), are believed to be involved in mediating this effect since it has been shown previously that depletion
of 5-HT or blockade of 5-HT receptors protects DBA/2J mice from these audiogenic seizures. The present study was undertaken
to determine whether antagonism of the newly identified 5-HT
7 receptor may protect DBA/2J mice from audiogenic seizures by attempting to correlate in vivo potency of compounds with their
affinity at the 5-HT
7 receptor. All compounds used in the correlation were shown to be antagonists at the 5-HT
7 receptor and a statistically significant correlation was observed between 5-HT
7 affinity and doses for half-maximal response (ED
50) for protection of DBA/2J mice from sound-induced seizures (
r = 0.80;
P < 0.05). No significant correlation was observed between in vivo activity and affinity at either 5-HT
1A, 5-HT
2A or 5-HT
2C receptors. It is also unlikely that interactions between the 5-ht
5 receptor will protect DBA/2J mice from audiogenic seizures since metergoline and mesulergine which are both active in this
in vivo model have no affinity for the 5-ht
5 receptor. There are similarities between the pharmacology of the 5-HT
7 receptor and that of the 5-HT
1A receptor, however the correlation between the in vivo potency in DBA/2J mice and 5-HT
1A affinity was not significant. Furthermore, the 5-HT
1A receptor antagonist WAY 100135 did not protect DBA/2J mice from audiogenic seizures at doses that antagonise 5-HT
1A receptor-mediated effects in mice. These data suggest that antagonism of 5-HT
7 receptors may protect against audiogenic seizures in DBA/2J mice although a definitive conclusion must await studies with
selective 5-HT
7 antagonists.
Received: 20 March 1997 / Accepted: 10 August 1997
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