Morphine reversed formalin-induced CA1 pyramidal cell suppression via an effect on septohippocampal neural processing

Abstract

We have investigated the effect of morphine on (i) dorsal hippocampus field CA1 nociceptive response to a formalin injection, and (ii) septohippocampal neural processing. Extracellular recordings were made in urethane (1.0 g/kg)-anaesthetized rats. Previously, we reported that formalin (5%, 0.05 ml, s.c.) injection into a hindpaw evoked, in the CA1 field, a 'signal-to-noise processing', i.e. a selective excitation of a few pyramidal cells with high spontaneous extracellular activity against a background of widespread pyramidal cell suppression accompanied by an increase in period of rhythmic slow activity. In the present study, morphine administered i.p. concurrent to a formalin injection reversed the pyramidal cell suppression in conjunction with a decrease in the period of evoked rhythmic slow activity. The effect was dose dependent and was prominent at the dose of 5 mg/kg. This dose, administered as a pretreatment, also truncated CA1 pyramidal cell suppression or excitation to a formalin injection. Furthermore, the drug decreased the power and frequency of the posterior hypothalamus- supramammillary region stimulation-evoked hippocampal field CA1 rhythmic slow activity. Such an effect was observed in a time-frame parallel to the decline in the period of formalin injection-induced field CA1 rhythmic slow activity. However, morphine sulphate administration per se did not alter pyramidal cell excitability or extracellular activity. Together, the above findings are consistent with the notion that morphine influences dorsal hippocampus field CA1 pyramidal cell suppression partly via an effect on the septohippocampal neural processing. However, the effect of the drug does not involve a change in the pyramidal cell basal extracellular responses. The effect of morphine on septohippocampal neural processing might be functionally relevant to the influence of the drug on the affective-motivational component of pain.