Differential effects of acute methamphetamine on synaptic plasticity

Anita Jeyakumar, Tennessee State University


The synergistic activation of dopaminergic synapses appears to be necessary for maintenance of long-term potention (i.e., late-phase LTP), a form of synaptic plasticity taken to be a cellular correlate of memory consolidation. We report here the dose-dependent effects of methamphetamine, a drug that increases release of amines, on the production of late-phase LTP. Briefly, bioelectrical recordings were obtained from male guinea pigs (150-200g) pre-treated with saline, low methamphetamine (1mg/kg) or high methamphetamine (10mg/kg). Two hours after drug treatment, guinea pigs were anesthetized with urethane (1500mg/kg IP) and prepped for recordings. Small access holes were made in the skull to allow for stereotaxic placement of electrodes in the ipsilateral CA3, ipsilateral CA1, and contralateral CA1 regions. Then ipsilateral CA3 afferents were activated (50-150$\mu$A for 0.1ms, 0.02Hz) to evoke baseline population spikes (05-01mV) in both CA1 regions. It was found that tetanic stimuli (100Hz, 1s; 3 trains at 5s intervals) produced late-LTP that was sustained over 3 hours, in saline (2 of 3), and in low methamphetamine (3 of 3) guinea pigs. In contrast, late-LTP did not occur in guinea pigs treated with high methamphetamine (3 of 3). Molecular studies showed that GAP-43 production occurred in animals with LTP, and low methamphetamine but more so with high methamphetamine. Presuming the effects of methamphetamine were mediated via increased release of dopamine, our results suggest that there may be a "threshold" due to GAP-43 production beyond which excessive activation of dopaminergic system, as probably occurs with high methamphetamine, results in antagonism of late-LTP development.

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Recommended Citation

Anita Jeyakumar, "Differential effects of acute methamphetamine on synaptic plasticity" (1999). ETD Collection for Tennessee State University. Paper AAI1396146.