Dopamine Agonists Increase Nitric Oxide Production in the Paraventricular Nucleus of the Hypothalamus: Correlation with Penile Erection and Yawning

Abstract

A low dose of apomorphine (80 micrograms/kg s.c.), a mixed D1/D2 agonist that induces penile erection and yawning, increased the concentration of NO2-from 1.12 +/- 0.45 microM to 3.8 +/- 0.75 microM and NO3-from 5.53 +/- 0.82 to 11.25 +/- 2.30 microM in the dialysate collected from the paraventricular nucleus of the hypothalamus of male rats by in vivo microdialysis. The NO2-concentration was also increased by LY 171555 (50 micrograms/kg s.c.), a D2 agonist that induces penile erection and yawning, but not by SKF 38393 (5 mg/kg s.c.), a D1 agonist with no effect on these responses. Conversely, apomorphine's effect on NO2-was prevented by haloperidol (0.5 mg/kg i.p.), a mixed D1/D2 antagonist and L-sulpiride (25 mg/kg i.p.), a D2 antagonist, but not by the D1 agonist SCH 23390 (50 micrograms/kg s.c.), although all three compounds prevented penile erection and yawning. The apomorphine effect on NO2-, penile erection and yawning was also prevented by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (200 micrograms i.c.v.). The nitric oxide scavenger haemoglobin (200 micrograms i.c.v.) also prevented the NO2-increase, but was ineffective against penile erection and yawning. In contrast, the oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin (1 microgram i.c.v.) and the guanylate cyclase inhibitor methylene blue (300 micrograms i.c.v.) had no effect on the NO2-increase, but did prevent the behavioural responses. We infer from this that dopamine agonists induce penile erection and yawning by acting on D2 receptors that increase nitric oxide synthase activity in the cell bodies of paraventricular oxytocinergic neurons projecting to extra-hypothalamic brain areas.

Sexual behavior in male rodents

“…GABA and opioids inhibit these processes. This laboratory has also shown that DA (Melis et al, 2003), glutamate, , and NO (Melis et al, 1998) are released in the PVN during copulation.…”

The Blunted Plasma Cortisol Response to Apomorphine and Its Relationship to Treatment Response in Patients with Schizophrenia

“…Nitric oxide (NO) is of interest in this regard since there is considerable evidence that it has an inhibitory effect on corticosterone secretion and that apomorphine enhances NO formation (Melis et al 1996). NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, has been reported to increase basal ACTH and corticosterone secretion in rodents (Adams et al 1992;Giordano et al 1996).…”

Neurotransmitters: central and peripheral mechanisms

“…In addition, NO seems to be involved, since apomorphine (given s.c.) increased NOS activity and NO production in the paraventricular nucleus. 20 Both the increase in NO and the erectile response to apomorphine were reduced by NOS inhibition.…”