Pressure ejection of drugs on single neurons in vivo: Technical considerations and application to the study of estradiol effects.

Through multibarrelled microelectrodes, simultaneous extracellular unit recording, microniotophoretic application of glutamate and pressure ejection of picoliter volumes of steroid hormones were carried out in order to study the effects of estradiol on spontaneous and glutamate-induced activity in the female guinea-pig brain. Preliminary were undertaken to ascertain the reliability of the method. Reversible and dose-dependent unspecific fluid effects inhibited the neuron discharge. These effects were mainly observed when the discharge was induced by glutamate and also occurred on spontaneous activity. A control procedure was adopted to avoid fluid effects when testing steroid hormones. Recordings from 280 septopreoptic neurons indicated that local application of estradiol increased (13.93%) or decreased (3.93%) the discharge frequency. Responses were elicited within 30 sec after the pressure was turned on. This finding suggests a direct hormonal action on membrane functioning. In addition, the effects of pressure-applied cortisol were tested on 13 estradiol-sensitive neurons. Two neurons discriminated between the two hormones whereas 11 responded in a very similar manner. These results are discussed in terms of the stereoselectivity of the steroid-sensitive neurons.