Glutamatergic ionotropic blockade within accumbens disrupts working memory and might alter the endocytic machinery in rat accumbens and prefrontal cortex.

Effects of blocking N-methyl-D-aspartic acid (NMDA) and non-NMDA glutamatergic receptors on performance in the hole board test was studied in male rats bilaterally cannulated into the nucleus accumbens (Acc). Rats, divided into 5 groups, received either 1 microl injections of saline, (+/-) 2-amino-7-phosphonoheptanoic acid (AP-7) (0.5 or 1 microg) or 2,3-dioxo-6-nitro-1,2,3,4,tetrahydrobenzo-(f)quinoxaline-7-sulphonamide disodium (NBQX, 0.5 or 1 microg) 10 min before testing. An increase by AP-7 was observed in ambulatory movements (0.5 microg; p < 0.05), non-ambulatory movements and number of movements (1 microg; p < 0.05); sniffing and total exploration (1 microg; p < 0.01). When holes were considered in order from the first to the fifth by the number of explorations, the most visited holes (first and second) of the AP-7 group were significantly higher than the corresponding holes of saline group (p < 0.05 for 0.5 microg and p < 0.001 for 1 microg). When the second hole was compared with the first of his group, a difference was only observed in the AP-7 1 microg group (p < 0.001). Increasing differences between the other holes and the first were observed by drug treatment. At molecular level, it was observed that AP-7 induced an increase of the coat protein AP-2 expression in Acc, but not AP-180 neither the synaptic protein synaptophysin. The increase of AP-2 was also observed in the medial prefrontal cortex by the action of AP-7 but not NBQX. We conclude that NMDA glutamatergic blockade might induce an activation of the endocytic machinery into the Acc, leading to stereotypies and perseverations, lacking cortical intentional direction.

Prazosin blocks the glutamatergic effects of N-methyl-D-aspartic acid on lordosis behavior and luteinizing hormone secretion in the estrogen-primed female rat

We have observed that intracerebroventricular (icv) injection of selective N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptor antagonists inhibits lordosis in ovariectomized (OVX), estrogen-primed rats receiving progesterone or luteinizing hormone-releasing hormone (LHRH). When NMDA was injected into OVX estrogen-primed rats, it induced a significant increase in lordosis. The interaction between LHRH and glutamate was previously explored by us and another groups. The noradrenergic systems have a functional role in the regulation of LHRH release. The purpose of the present study was to explore the interaction between glutamatergic and noradrenergic transmission. The action of prazosin, an alpha1- and alpha2b-noradrenergic antagonist, was studied here by injecting it icv (1.75 and 3.5 µg/6 µL) prior to NMDA administration (1 µg/2 µL) in OVX estrogen-primed Sprague-Dawley rats (240-270 g). Rats manually restrained were injected over a period of 2 min, and tested 1.5 h later. The enhancing effect induced by NMDA on the lordosis/mount ratio at high doses (67.06 ± 3.28, N = 28) when compared to saline controls (6 and 2 µL, 16.59 ± 3.20, N = 27) was abolished by prazosin administration (17.04 ± 5.52, N = 17, and 9.33 ± 3.21, N = 20, P < 0.001 for both doses). Plasma LH levels decreased significantly only with the higher dose of prazosin (1.99 ± 0.24 ng/mL, N = 18, compared to saline-NMDA effect, 5.96 ± 2.01 ng/mL, N = 13, P < 0.05). Behavioral effects seem to be more sensitive to the alpha-blockade than hormonal effects. These findings strongly suggest that the facilitatory effects of NMDA on both lordosis and LH secretion in this model are mediated by alpha-noradrenergic transmission.

Prazosin blocks the glutamatergic effects of N-methyl-D-aspartic acid on lordosis behavior and luteinizing hormone secretion in the estrogen-primed female rat.

We have observed that intracerebroventricular (icv) injection of selective N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptor antagonists inhibits lordosis in ovariectomized (OVX), estrogen-primed rats receiving progesterone or luteinizing hormone-releasing hormone (LHRH). When NMDA was injected into OVX estrogen-primed rats, it induced a significant increase in lordosis. The interaction between LHRH and glutamate was previously explored by us and another groups. The noradrenergic systems have a functional role in the regulation of LHRH release. The purpose of the present study was to explore the interaction between glutamatergic and noradrenergic transmission. The action of prazosin, an alpha1- and alpha2b-noradrenergic antagonist, was studied here by injecting it icv (1.75 and 3.5 microg/6 microL) prior to NMDA administration (1 microg/2 microL) in OVX estrogen-primed Sprague-Dawley rats (240-270 g). Rats manually restrained were injected over a period of 2 min, and tested 1.5 h later. The enhancing effect induced by NMDA on the lordosis/mount ratio at high doses (67.06 +/- 3.28, N = 28) when compared to saline controls (6 and 2 microL, 16.59 +/- 3.20, N = 27) was abolished by prazosin administration (17.04 +/- 5.52, N = 17, and 9.33 +/- 3.21, N = 20, P < 0.001 for both doses). Plasma LH levels decreased significantly only with the higher dose of prazosin (1.99 +/- 0.24 ng/mL, N = 18, compared to saline-NMDA effect, 5.96 +/- 2.01 ng/mL, N = 13, P < 0.05). Behavioral effects seem to be more sensitive to the alpha-blockade than hormonal effects. These findings strongly suggest that the facilitatory effects of NMDA on both lordosis and LH secretion in this model are mediated by alpha-noradrenergic transmission.

Blockade of pro-oestrus LH surge and ovulation by GABA increase in the rat locus coeruleus.

The effects of gamma-aminobutyric acid (GABA) increase at the nucleus locus coeruleus (LC) on pro-oestrus LH release and ovulation were evaluated in rats. Local microinjection of the GABA-transaminase inhibitor gamma-vinyl-GABA (GVG) produced 6 h later a marked increase in GABA in the LC. Such action caused a significant decrease of plasma LH levels and prevented the pro-oestrus LH surge. In some animals, plasma prolactin levels were also lowered, but in others its plasma concentrations were high and similar to that in controls. Ovulation did not occur in the rats treated with GVG. In additional experiments, the periventricular gray substance (PGS) close to the locus coeruleus was injected with GVG. Results obtained show a LH surge blockade and failure of ovulation in most of these rats. These findings may be interpreted on the basis of GABA action on rostral LC cells that project to the PGS. The results altogether suggest that through neurons of the locus coeruleus, GABA may exert an inhibitory role in the regulation of LH secretion.