Coordinate regulation of the cyclic AMP system with firing rate and expression of tyrosine hydroxylase in the rat locus coeruleus: effects of chronic stress and drug treatments.
Recent studies have demonstrated that chronic stress increases the firing rate and expression of tyrosine hydroxylase (TH) in neurons of the locus coeruleus (LC), the major noradrenergic nucleus in brain. The present study was undertaken to examine the influence of chronic stress and other treatments known to influence the activity of LC neurons on the cyclic AMP (cAMP) second messenger system in these neurons. Chronic (5 days) cold exposure significantly increased levels of TH immunoreactivity in the LC, as previously reported, but not in substantia nigra (SN) or ventral tegmentum (VT), two dopaminergic nuclei studied for comparison. Chronic cold exposure increased levels of cAMP-dependent protein kinase activity in soluble, but not particulate, fractions of the LC, and increased basal and GTP- and forskolin-stimulated adenylate cyclase activity in this brain region. In contrast, levels of the protein kinase and adenylate cyclase in VT, SN, and frontal cortex were not significantly influenced by cold exposure. To study further the relationship between regulation of LC firing rate, TH expression, and the cAMP system in the LC, other treatments known to influence TH were examined. Reserpine treatment, shown previously to increase levels of TH, was found to increase both LC firing rate and levels of soluble cAMP-dependent protein kinase activity in the LC. 6-Hydroxydopamine, shown previously to increase levels of TH and firing rate of LC neurons, also increased soluble levels of protein kinase activity. Other treatments known to either increase (adrenalectomy) or decrease (chronic imipramine) levels of TH in the LC were also found to increase or decrease, respectively, levels of cAMP-dependent protein kinase activity in this brain region.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508.
K R
KR
Melia
K
K
Rasmussen
R Z
RZ
Terwilliger
J W
JW
Haycock
E J
EJ
Nestler
R S
RS
Duman
D000315:Adrenalectomy; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002908:Chronic Disease; D000242:Cyclic AMP / Q000378:metabolism*; D004594:Electrophysiology; D008125:Locus Coeruleus / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000172:deficiency; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology*; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D000928:Antidepressive Agents; D012110:Reserpine; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine