Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA270

Poster Communications

Chronic Methamphetamine Alters Neural Oscillations and Synaptic Plasticity in the Hippocampus in Guinea Pigs, in vivo

A. D. Aduonum1, J. Locigno1, S. Chirwa2

1. Biomedical Sciences, GA Campus - Philadelphia College of Osteopathic Medicine, Suwanee, Georgia, United States. 2. Neuroscience and Pharmacology, Meharry Medical College, Nashville, Tennessee, United States.

Methamphetamine (METH) is a highly addictive psychostimulant that affects the brain's memory consolidation processes. Studies show that chronic METH users perform poorly than controls on tasks of verbal and nonverbal memory, recognition, attention, and decision-making. Previous studies by Aduonum and co-workers (2001) found that acute low doses of METH (1 mg/kg IP) facilitated long-term potentiation (LTP, i.e. enduring increase in synaptic efficacy in the hippocampus taken to be the cellular correlate for learning and memory), whereas high doses of METH (10 mg/kg IP) attenuated LTP maintenance. However, the neural mechanism through which METH altered LTP and, therefore, memory consolidation still remain unclear. Within this context, the present study aimed to investigate the effect of chronic high dose METH (10 mg/kg-similar to abused doses) treatment on changes in neural circuit oscillations and synaptic plasticity linked to memory consolidation. We treated twenty male Wistar guinea pigs (3-4 weeks old; weight, 200-250 g) from Charles River Laboratory with 10 mg/kg/day METH (N=12) or phosphate buffered saline (PBS, N= 8) for 7 days. Drugs were administered as a continuous infusion using ALZET mini-pumps (Model 2001). After 7 days of treatment a subset of guinea pigs from each group (METH = 6 and PBS = 4) were anesthetized with urethane (1500 mg/kg) and prepared for electrophysiological recordings. Briefly, small access holes were made in the skull through which bipolar Tungsten electrodes were lowered. Low frequency stimulation (100-120 μA, 0.25 ms, at 0.1 Hz) was applied to the left CA3 and local field potentials and evoked population spikes recorded in ipsilateral CA1 region, in vivo. Subsequently, high frequency stimulation (HFS; 100 Hz, 1 sec, 3 trains) was applied to the CA3 region to induce LTP in CA1. Similar recordings were conducted in the remaining subset of guinea pigs (METH = 6 and PBS = 4) after 7 days of drug washout. All evoked responses were amplified at a gain of 1000x filtered at a bandpass of 100 Hz - 5 kHz and analyzed with Clampfit 10.6. We found that METH-treated guinea pigs exhibited increased spontaneous CA1 cell discharges and had diminished slow wave oscillations. By contrast, PBS controls exhibited fewer spontaneous discharges and had prominent slow wave oscillations whose peak were inundated with robust ‘ripples', a hallmark of transfer of information from the hippocampus to neocortical structures. We also found that LTP, a cellular correlate of learning and memory was attenuated in the METH-treated guinea pigs when compared to PBS controls. The effects of METH on CA1 cell discharges, oscillations and LTP were still present even after the 7-day washout. Taken together, our results raise the possibility that METH-induced changes in CAI network properties may partly underlie the reported memory impairments associated with the drug.

Where applicable, experiments conform with Society ethical requirements