Psychostimulants such as amphetamine and cocaine mediate their effects, at least in part, via the dopamine neurotransmitter system. The hippocampus contains all five (D1-D5) subtypes of dopamine receptors and modulation of dopamine function has been reported to have a wide variety of effects, including alterations in excitatory and inhibitory synaptic transmission, and electrical coupling via gap junctions. Several different types of synchronized network activity have been described in the hippocampus that depend upon both synaptic interactions and gap junction-dependent electrical transmission. We therefore wished to determine what effect amphetamine and cocaine might have on the generation of rhythmic activity in the hippocampus.

Hippocampal slices (450 mm thick) were prepared from adult, male Wistar rats terminally anaesthetised with inhaled isoflurane and injection (I.M.) of ketamine (▓ge│ 100 mg kg^-1) and xylazine (▓ge│ 10 mg kg^-1). Animals were perfused transcardially with artificial cerebrospinal fluid (ACSF) in which NaCl was replaced with equimolar sucrose. Slices were maintained in an interface recording chamber perfused with ACSF and oxygenated with 95 % O₂ and 5 % CO₂ at 34 °C. Extracellular field recordings were made in stratum radiatum or stratum pyramidale of the CA3 and CA1 regions. Changes in oscillatory activity were assessed by measuring the area between 20 and 80 Hz from the power spectra. Data are expressed as means ± S.E.M. Bath application of kainate (300 nM) elicits a persistent λ frequency oscillation that depends upon both excitatory and inhibitory synaptic interactions. Amphetamine sulphate (10-30 mM) caused a mean decrease of 53 ± 32 % in the power of the gamma frequency activity (n = 8). This reduction was reversible on washout of amphetamine. Application of cocaine also elicited a reduction in the kainate-evoked λ frequency activity with a mean decrease of 70 ± 11.8 % (n = 6). We also assessed the effect of amphetamine on ultrafast oscillations (80-200 Hz) that occur in the absence of synaptic transmission and depend upon electrical transmission via gap junctions. However, fast oscillatory activity (evoked by pressure ejection of potassium in the presence of blockers of fast glutamaterigc and GABA_Aergic transmission) persisted in the presence of amphetamine. The same duration application of amphetamine failed to reduce the power of the fast oscillation (11.3 ± 1.4% n = 3). This result suggests that amphetamine selectively reduces kainate-evoked oscillations but does not affect the gap junction-dependent fast oscillatory activity. In conclusion, some of the well-known effects of psychostimulants, such as those on attentional mechanisms, may be due to effects on cortical network activity.

This work was funded by the MRC.

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