Research ReportDopaminergic transmission in the midbrain ventral tegmental area in the induction of hippocampal theta rhythm

- D2 autoreceptors blockade in the VTA by flupenthixol induced hippocampal theta rhythm.
- Microinjections of amphetamine into the VTA elicited theta rhythm.
- Increased release of dopamine from the VTA appears to induce hippocampal theta.

Hippocampal rhythmic slow activity (RSA, theta) is regulated by many brainstem structures, including the midbrain ventral tegmental area (VTA). This work aimed at assessing the role of the dopaminergic (DA) transmission of the VTA in this regulation. Male Wistar rats (n=35) in urethane anaesthesia received an intra-VTA microinjection of either flupenthixol (FLU; doses of 5.0, 2.5, 1.25 and 0.625 μg) or amphetamine (AMPH; 2.5 and 5.0 μg) following control solvent microinjection. Peak power (Pmax) and corresponding peak frequency (Fmax) for delta and theta bands were extracted from EEG recording. Flupenthixol at a dose of 1.25 μg evoked long-lasting theta, continuing for 32.0 min on average, with a mean latency of 7.1 min. Other doses of FLU caused an increase of Pmax theta and reduction of Pmax delta without generating visually recognizable, regular theta rhythm. 5 μg of AMPH evoked theta continuing for 24.4 min on average, with a mean latency of 9.7 min. The lower dose was much less effective, with its outcome resembling the one after the less active FLU doses. During pharmacologically induced theta rhythm, both after FLU and AMPH, brief episodes of asynchronous activity appeared periodically, and they were more frequent and longer in AMPH groups. AMPH may act locally on multiple sites, inhibiting DA cells in somatodendritic region but also increasing dopamine release in target structures, and this, depending on AMPH dose, can lead to induction of theta rhythm. Locally administered DA antagonist on the other hand, when used at a proper dose, can produce theta most likely by the mechanism of inhibiting autoreceptors.