Hippocampal noradrenergic neurotransmission in concurrent EEG desynchronization and inhibition of penile erection induced by cocaine in the rat

Abstract

We previously reported that cocaine may induce activation of cortical (cEEG) and hippocampal (hEEG) electroencephalographic signals, concurrent with inhibition of penile erection, via an action on the hippocampal formation. The present study further evaluates the role of noradrenergic neurotransmission at the hippocampal formation in this process, using adult, male Sprague-Dawley rats anaesthetized and maintained by chloral hydrate. Unilateral microinjection of cocaine (100 nmoles) into the hippocampal CA1 or CA3 subfield or dentate gyrus elicited significant activation of both cEEG and hEEG activity. At the same time, the intracavernous pressure (ICP), our experimental index for penile erection, underwent a discernible reduction. Co-administration of equimolar doses (250 pmoles) of prazosin, naftopidil, yohimbine or rauwolscine significantly reversed those effects elicited by cocaine on cEEG, hEEG and ICP. Microinjection unilaterally of equimolar doses (5 nmoles) of norepinephrine, phenylephrine or BHT 933 into the hippocampal formation, similar to cocaine, also induced appreciable cEEG and hEEG excitation, with a simultaneous decrease in ICP. We conclude that cocaine may activate cEEG and hEEG and decrease ICP via noradrenergic neurotransmission, possibly engaging at least alpha(1A/D)-, alpha(2B)- and alpha(2C)-adrenoceptors at the hippocampal formation.

Figure 1

Illustrative example of the temporal effects of microinjection unilaterally into the hippocampal formation of cocaine (100 nmoles, at arrow), together with aCSF, on electroencephalographic signals recorded from the somatosensory cortex (cEEG) or hippocampal formation (hEEG), and their respective root mean square (cRMS or hRMS) and mean power frequency (cMPF or hMPF) values. Also shown are concurrent responses to cocaine of intracavernous pressure (ICP).

Figure 2

Maximal effects on root mean square (RMS) or mean power frequency (MPF) values of cortical or hippocampal electroencephalographic (cEEG or hEEG) signals and intracavernous pressure (ICP) of microinjection unilaterally into the hippocampal formation of cocaine (Coc, 100 nmoles), together with equimolar concentrations (250 pmoles) of prazosin (Pra), naftopidil (Naf), yohimbine (Yoh), rauwolscine (Rau), aCSF or 20% methanol (MeOH). The maximal values measured during 10 min of baseline recording and within 30 min after administration of Coc-Pra, Coc-Naf, Coc-Yoh, Coc-Rau, Coc-aCSF or Coc-MeOH are presented as mean±s.e.mean, n=5–7 animals per group. ^*P<0.05 vs baseline values in the Dunnett analysis. ⁺P<0.05 vs the corresponding Coc-aCSF or Coc-MeOH group in the Scheffé analysis.

Figure 3

Maximal effects on root mean square (RMS) or mean power frequency (MPF) values of cortical or hippocampal electroencephalographic (cEEG or hEEG) signals and intracavernous pressure (ICP) of microinjection unilaterally into the hippocampal formation of equimolar concentrations (5 nmoles) of norepinephrine (NE), phenylephrine (Phe), BHT 933 (BHT) or aCSF. The maximal values measured during 10 min of baseline recording and within 30 min after administration of the agonists or aCSF are presented as mean±s.e.mean, n=5–7 animals per group. ^*P<0.05 vs baseline values in the Dunnett analysis, and ⁺P<0.05 vs aCSF group in the Scheffé analysis.

Figure 4

Diagrammatic representation of the hippocampal formation at two rostral-caudal levels showing the location of sites in the CA1 or CA3 subfield or dentate gyrus (DG) where microinjection of test agents or vehicle was delivered (left side); or hEEG signals were recorded (right side). For clarity, only 25% of the total microinjection or recording sites are included. Numbers on the right side of each diagram represent the distance from the bregma.