Abstracts

RATIONALE: In this study the role of adenosine A1 receptors of CA1 region of the hippocampus on amygdala kindled seizures was investigated in rats. Results obtained showed that in kindled animals, bilateral injection of N6-cyclohexyladenosine (CHA), an adenosine A1 receptor agonist, at doses of 0.1, 1 and 10 micromolar into the CA1 region of the hippocampus significantly decreased the afterdischarge duration and stage 5 seizure duration and increased the latency to stage 4 seizure, but there were no changes in seizure stage. Also, bilateral injection of 1,3-dimethyl-8-cyclopenthylxanthine (CPT), an adenosine A1 receptor antagonist, at doses of 0.5 and 1 micromolar into the CA1 region of the hippocampus could not produce any changes in the seizure parameters. Intrahippocampal pretreatment of CPT (1 micromolar) before CHA (0.1 and 1 micromolar), reduced the effects of CHA on seizure parameters significantly. Thus, it may be suggested that CA1 region of the hippocampus plays an important role in spreading seizure spikes from the amygdala to other brain regions and activation of adenosine A1 receptors in this region, participates in anticonvulsant effects of adenosine agonists.
METHODS: Materials and methods
2.1. Surgical and kindling procedure
Sprague-Dawley rats were stereotaxically implanted with bipolar stimulation and monopolar recording electrodes terminating in the basolateral amygdala of the right hemisphere and two 23 gauge guide cannulae also implanted in the CA1 regions of the dorsal hippocampi.
One week after surgery, AD threshold was determined in the amygdala by a 2 s, 60 Hz monophasic square wave stimulus of 1 ms per wave. In the kindled animals, the recorded parameters were: seizure stage (SS), amygdala AD duration (ADD), the latency to the onset of bilateral forelimb clonus (S4L) and the duration of stage 5 (S5D).
2.2. Drug administration
For intrahippocampal injection, CHA and CPT were dissolved in artificial cerebrospinal fluid (ACSF). . Drugs were infused via two 30 gauge cannulae which extended 1 mm below the tip of the guide cannulae.
2.3. Intrahippocampal CHA or CPT
CHA at concentrations of 0.01, 0.1, 1 and 10 micromolar or CPT at concentrations of 0.5 and 1 micromolar were infused in situ and 5, 15, and 60 min later animals were stimulated at AD threshold.
2.4. Intrahippocampal CHA with CPT
2.6. Statistical analysis
2.6.1-A two way ANOVA and Tukey[ssquote]s post test was done to compare different groups of animals at different times post different doses of drug injections.
2.6.2-student[ssquote]s t-test.
RESULTS: All amygdala-kindled rats responded with stable stage 5 seizure in either a non-infusion condition or after ACSF infusion and there was not any effect of ACSF injection on seizure parameters.
At the doses employed, CHA and CPT had no noticeable effect on behavioral or locomotor activity with respect to predrug or ACSF infused rats.
CONCLUSIONS: Results obtained in this study showed that bilateral injection of CHA into the CA1 region of the hippocampus has anticonvulsant effects on amygdaloid kindled seizures.
[Supported by: Tarbiat Modarres University]