An electrophysiological and neuroanatomical study of the medial prefrontal cortical projection to the midbrain raphe nuclei in the rat

136

It has previously been shown that inescapable (IS) but not escapable (ES) stress potentiates the rewarding properties of morphine as measured by conditioned place preference and psychomotor activation, and that this potentiation may be mediated by dorsal raphe nucleus (DRN) serotonin (5-HT) neurons. The medial prefrontal cortex (mPFC) has been implicated in both reward and stress, and is a projection region of the DRN. The mPFC also contains dopaminergic afferents from the ventral tegmental area, which has been the focus of many studies exploring both the rewarding properties of drugs and the aversive properties of stress. The role of the mPFC in stress/ drug reactivity interactions is largely unknown. The present study usedin vivo microdialysis to examine 5-HT and dopamine (DA) efflux in the mPFC of rats during IS, ES or no stress (NS). IS and ES rats received the stressor in yoked pairs. The stressor consisted of tailshocks that could be terminated for both rats by the ES rats. Large increases in 5-HT and DA levels were observed during IS but not ES or NS. DA and 5-HT efflux were also measured 24 h later in the same rats in response to morphine (3 mg/kg) or saline. Sustained increases in 5-HT levels were observed after morphine in rats that had previously received IS but not in rats that had received ES or NS. No changes in DA efflux were observed after morphine. Thus, 5-HT and DA in the mPFC may be involved in stressor controllability effects, and the sensitization of 5-HT neurons by IS extends to the mPFC and to morphine as a challenge.

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Stressor Controllability Modulates Stress-Induced Dopamine and Serotonin Efflux and Morphine-Induced Serotonin Efflux in the Medial Prefrontal Cortex

Bland

Hargrave

Pepin

et al. 2003

136

“…Thus, in line with previous reports (Moghaddam et al, 1997;Adams and Moghadam, 2001;Lorrain et al, 2003), MK-801 increases glutamate release onto AMPA/kainate receptors, which, in turn, elicit an enhanced glutamatergic output from mPFC neurons, including those projecting to the dorsal raphe nucleus, thereby increasing serotonergic cell firing and cortical 5-HT efflux. Although this functional interplay between the mPFC and the dorsal raphe nucleus is well documented (Hajós et al, 1998;Celada et al, 2001;Martín-Ruiz et al, 2001;Amargós-Bosch et al, 2003;Lucas et al, 2005), we presently cannot rule out the possibility of a direct effect of MK-801 on serotonergic neurons of the dorsal raphe nucleus (Callado et al, 2000;Tao and Auerbach, 2000) and its blockade downstream by NBQX acting on AMPA receptors putatively located in serotonergic terminals Effect of clozapine and haloperidol X Ló pez-Gil et al (Maione et al, 1997). With regard to glutamate, however, although presynaptic AMPA receptors have been described in striatal glutamatergic axon terminals (Patel et al, 2001;Fujiyama et al, 2004), they do not seem to be present in the cortical counterparts (Fujiyama et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

López-Gil

Babot

Amargós-Bosch

et al. 2007

170

162

The administration of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine and ketamine has been shown to increase the extracellular concentration of glutamate and serotonin (5-HT) in the medial prefrontal cortex (mPFC). In the present work, we used in vivo microdialysis to examine the effects of the more potent noncompetitive NMDA receptor antagonist, MK-801, on the efflux of glutamate and 5-HT in the mPFC, and whether the MK-801-induced changes in the cortical efflux of both transmitters could be blocked by clozapine and haloperidol given systemically or intra-mPFC. The systemic, but not the local administration of MK-801, induced an increased efflux of 5-HT and glutamate, which suggests that the NMDA receptors responsible for these effects are located outside the mPFC, possibly in GABAergic neurons that tonically inhibit glutamatergic inputs to the mPFC. The MK-801-induced increases of extracellular glutamate and 5-HT were dependent on nerve impulse and the activation of mPFC AMPA/ kainate receptors as they were blocked by tetrodotoxin and NBQX, respectively. Clozapine and haloperidol blocked the MK-801-induced increase in glutamate, whereas only clozapine was able to block the increased efflux of 5-HT. The local effects of clozapine and haloperidol paralleled those observed after systemic administration, which emphasizes the relevance of the mPFC as a site of action of these antipsychotic drugs in offsetting the neurochemical effects of MK-801. The ability of clozapine to block excessive cortical 5-HT efflux elicited by MK-801 might be related to the superior efficacy of this drug in treating negative/cognitive symptoms of schizophrenia.

“…Single units were recorded from the medial septum and vertical limb of the diagonal band of Broca (MS/DBv; coordinates: 0.2 mm anterior to bregma, lateral 0 mm and 5-7 mm below the dura; Paxinos and Watson, 1986) using glass microelectrodes filled with 2M NaCl (impedance 10-20 MO). Extracellularly recorded potentials were amplified, filtered, displayed, discriminated and recorded for off-line analysis using conventional electrophysiological methods (Hajós et al, 1998). Neuronal activity was followed by constructing firing rate, frequency and interspike interval histograms using Spike3 program (Cambridge Electronic Design, Cambridge, UK).…”

Section: Electrophysiological Experimentsmentioning

confidence: 99%

Norepinephrine but not Serotonin Reuptake Inhibitors Enhance Theta and Gamma Activity of the Septo-Hippocampal System

Hajós¹,

Hoffmann²,

Robinson³

et al. 2002

Current neurobiological concepts attribute a central role of the hippocampal formation in cognitive and affective processes. Recent studies indicate that the hippocampus is affected in human depression, and antidepressant drugs induce hippocampal adaptive changes that are thought to be associated with their therapeutic action. In the present study, we investigated the action of various antidepressant drugs on the activity of the septo-hippocampal system, its oscillatory activity in particular. The acute effects of the norepinephrine (NE) reuptake inhibitors reboxetine and desipramine, and the selective serotonin reuptake inhibitor fluvoxamine were evaluated. Extracellular single-unit recordings were performed from the medial septum/diagonal band of Broca (MS/DBv), with simultaneous hippocampal EEG recordings of anesthetized rats. Systemic administration of reboxetine synchronized hippocampal EEG, resulting in a significant increase in power at theta frequency, and an increase in frequency and power of gamma-wave activity. Parallel to EEG synchrony, reboxetine induced or enhanced theta oscillation of MS/DBv neurons. Oscillatory frequencies of MS/DBv neurons were identical, and phase locked to the corresponding hippocamapal theta frequencies. Under the same experimental conditions, reboxetine induced a two-fold increase in extracellular NE (but not serotonin) levels in the hippocampus as revealed by microdialysis. Desipramine, but not the serotonin reuptake inhibitor fluvoxamine, evoked responses similar to those of reboxetine regarding septo-hippocampal theta activity. The present findings indicate that even though both NE and serotonin reuptake inhibitors are clinically effective antidepressant drugs, their action on the septo-hippocampal oscillatory behavior is different. It is presumed that selective NE reuptake inhibitors could modulate various cognitive processes associated with hippocampal oscillatory activity.