Abstracts

Methamphetamine (METH), a schedule II drug, has long been known to be a potent releaser of dopamine and serotonin. In addition, seizures are often associated with acute METH overdose. The goal of this study was to assess whether multiple METH treatments affect rat amygdala kindling acquisition, which is a well-established model of epileptogenesis. Two groups of male Sprague-Dawley rats weighing between 260-280 grams (n=14 in METH-treated group, n=10 in control group) were employed. In the METH-treated group, multiple METH injections (4[times]10 mg/kg, s.c.) were administered every 2 hrs. The control group received saline (4[times]1 ml/kg, s.c.) every 2 hrs. Three days after the last treatment, bipolar stimulating-recording electrodes were implanted into the basolateral amygdala using stereotaxic surgery. After a one-week recovery period, individual afterdischarge thresholds (ADTs) were determined by stimulating the amygdala with increasing stimulus intensity beginning at 40 [mu]Amp and increasing by 20 [mu]Amp increments until an afterdischarge of at least 3 seconds was observed. This current was recorded as the ADT and considered reflective of each animal[apos]s electrographic seizure threshold. On the day following ADT determination each rat was stimulated at its individual ADT once per day until all rats in the control group displayed three consecutive secondarily generalized seizures (i.e., stage IV/V according to the Racine scale, 1972). Both behavioral scores and afterdischarge durations (ADDs) displayed a progressive increase with each kindling stimulation. There was no significant difference in ADT between the METH and saline groups. However, METH-treated rats displayed a faster rate of kindling as estimated by the number of stimulations required to reach stage 3 or stage 4/5 seizures. In METH-treated rats, 5.0[plusmn]0.3 and 8.3[plusmn]0.9 stimulations were required to reach 3 and stage 4/5 seizures, respectively; compared with 8.3[plusmn]0.9 and 11.6[plusmn]1.2 in control rats. The ADD was observed to be longer in the METH-treated group; nonetheless, the total ADD to reach either a stage 3 or stage 4/5 seizure was not significantly different between the two groups. Multiple METH treatment accelerates amygdala kindling acquisition. These results suggest that METH-induced neurotoxicity may contribute to epileptogenesis in susceptible individuals. (Supported by NIDA grant 5-PO1-DA 13367-04.)