Local Activation of Metabotropic Glutamate Receptors Inhibits the Handling‐Induced Increased Release of Dopamine in the Nucleus Accumbens but Not that of Dopamine or Noradrenaline in the Prefrontal Cortex: Comparison with Inhibition of Ionotropic Receptors

Abstract

On-line in vivo microdialysis was used to determine the effects of a 16-mm handling period on release of dopamine (DA) in the nucleus accumbens and of DA and noradrenaline (NA) in the medial prefrontal cortex of awake, freely moving rats. DA and NA were determined in one HPLC run. Handling resulted in an immediate and strong increase of both catecholamines in the prefrontal cortex. Maximal values for DA were 295%, and for NA 225%, of controls. DA in the nucleus accumbens was also increased (to 135% of controls) but only after a short delay. Local inhibition of ionotropic glutamate receptors by continuous reversed dialysis of the drugs 6-cyano-7-nitroquinoxaline, D-2-amino-5-phosphonopentanoic acid, or dizocilpine did not significantly affect handling-induced increases in cortical DA and NA release. Neither did the agonist of metabotropic glutamate receptors, trans-(1 S,3R)-1 -aminocyclopentane-1 ,3-dicarboxylic acid (ACPD), or the GABA-B agonist baclofen. Reversed dialysis of dizocilpine in the nucleus accumbens was equally ineffective, but ACPD inhibited the increase in DA release in this area. Stimulation of metabotropic glutamate receptors in the nucleus accumbens was previously reported to inhibit activation of DA release in that area after stimulation of glutamatergic or dopaminergic afferents. It is concluded that metabotropic receptors in the nucleus accumbens are important for the control of activation of DA release in the accumbens by physiological stimuli but that a similar mechanism is lacking in the prefrontal cortex.

Stimulation of group I mGlu receptors in the ventrotegmental area enhances extracellular dopamine in the rat medial prefrontal cortex

“…2a), extracellular DA increased in response to ICV injection of PBS. As rats were not habituated to handling before the experiment, this likely reflects the effect of handling/injection stress (Feenstra et al 1998;Peleg-Raibstein et al 2005). mGlu1 and mGlu5 receptor mRNA and immunoreactivity are widely distributed in the brain including the mPFC and midbrain (Shigemoto et al 1992;Romano et al 1995;Petralia et al 1997;Lavreysen et al 2004).…”

Acute Handling Stress Modulates Methylphenidate-induced Catecholamine Overflow in the Medial Prefrontal Cortex

“…In the same study, a non-NMDA glutamate receptor antagonist (DNQX) did not alter stressinduced changes in the mPFC NE overflow, whereas infusion of an NMDA glutamate receptor antagonist (CPP) reduced the stress-induced response of mPFC NE. Additionally, direct infusion of the GABA B agonist baclofen or glutamate receptor agonist and antagonists (ACPD, dixocilpine) into the mPFC did not alter stress-induced NE increases in this same region (Feenstra et al 1998). …”

“…Additionally, findings by Doherty and Gratton (1999) indicate that infusion of a GABA A agonist (muscimol) directly into the PFC inhibits stress-induced release of DA in the mPFC, while a GABA B antagonist (phaclofen) enhances this same release. On the contrary, under similar conditions Feenstra et al (Feenstra et al 1998) found no influence of the locally applied GABA B agonist baclofen or glutamate receptor agonists and antagonists (ACPD, dixocilpine) in the mPFC, although in an earlier study (Feenstra et al 1995) this group reported a benzodiazepine (diazepam) to inhibit the stress-induced release of DA in the mPFC. Taken together, these studies indicate that GABA B antagonism and GABA A agonism could play a possible role in the enhanced DAergic response to MP challenge in the mPFC induced by stress, although additional investigations would be required to support this hypothesis.…”

“…Dopamine (DA) and norepinephrine (NE) are two catecholamines shown to have increased release and utilization in the medial prefrontal cortex (mPFC) during stress Nakane et al 1994;Abercrombie et al 1989;Shimizu et al 1994). Numerous investigations have demonstrated preferential increases in mPFC DA overflow associated with stressful stimuli when compared with limbic regions (Abercrombie et al 1989;Ihalainen et al 1999;Feenstra et al 1998). This augmented response might be due to cross innervation of the mPFC from several brain stem projections, such as the A10 pathway from the ventral tegmental area (VTA) and/or noradrenergic connections from the locus coeruleus (LC).…”

Repetitive Transcranial Magnetic Stimulation Increases the Release of Dopamine in the Nucleus Accumbens Shell of Morphine-Sensitized Rats During Abstinence

“…Sham stimulation was applied as described above with the control rats receiving six trains of sham stimulation. As handling is known to be able to influence intracerebral DA release (Feenstra et al, 1998), control rats were treated in exactly the same way as the rTMS animals during all parts of the experiment.…”