Implications of Dedicated Seismometer Measurements on Newtonian-Noise Cancellation for Advanced LIGO.

Newtonian gravitational noise from seismic fields will become a limiting noise source at low frequency for second-generation, gravitational-wave detectors. It is planned to use seismic sensors surrounding the detectors' test masses to coherently subtract Newtonian noise using Wiener filters derived from the correlations between the sensors and detector data. In this Letter, we use data from a seismometer array deployed at the corner station of the Laser Interferometer Gravitational Wave Observatory (LIGO) Hanford detector combined with a tiltmeter for a detailed characterization of the seismic field and to predict achievable Newtonian-noise subtraction levels. As was shown previously, cancellation of the tiltmeter signal using seismometer data serves as the best available proxy of Newtonian-noise cancellation. According to our results, a relatively small number of seismometers is likely sufficient to perform the noise cancellation due to an almost ideal two-point spatial correlation of seismic surface displacement at the corner station, or alternatively, a tiltmeter deployed under each of the two test masses of the corner station at Hanford will be able to efficiently cancel Newtonian noise. Furthermore, we show that the ground tilt to differential arm-length coupling observed during LIGO's second science run is consistent with gravitational coupling.

Chronic administration of the antidepressants phenelzine, desipramine, clomipramine, or maprotiline decreases binding to 5-hydroxytryptamine2A receptors without affecting benzodiazepine binding sites in rat brain.

1. The effects of chronic administration of five antidepressant drugs on the benzodiazepine and 5-HT2A binding sites in the same rat brain were assessed. 2. Clomipramine, desipramine, maprotiline, fluoxetine, and phenelzine (all 10 mg/kg/day) were administered s.c. for 21 days by Alzet osmotic minipumps. 3. Results showed that none of the drugs changed the density or affinity of benzodiazepine binding sites, yet at the same dose all the drugs with the exception of fluoxetine decreased binding to 5-HT2A receptors in the same animals.

Chronic administration of the antidepressant phenelzine and its N-acetyl analogue: effects on GABAergic function.

The MAO inhibitor phenelzine (2-phenylethylhydrazine; PLZ) is used widely in psychiatry for the treatment of depression and panic disorder. Its N-acetyl metabolite, N2-acetylphenelzine (N2AcPLZ) is a reasonably potent nonselective inhibitor of monoamine oxidase (MAO) that causes elevation in brain levels of the biogenic amines. In the studies reported here, PLZ (0.05 mmol/kg/day), N2AcPLZ (0.10 mmol/kg/day) or vehicle were administered to male rats for 28 days s.c. with Alzet minipumps, and their effects on GABAergic function were examined. Whole brain concentrations of gamma-aminobutyric acid (GABA) were significantly elevated in the PLZ but not in the N2AcPLZ-treated group. PLZ was found to inhibit the anabolic enzyme glutamic acid decarboxylase (GAD) and, to a greater extent, the catabolic enzyme GABA transaminase (GABA-T). The results of these investigations suggest that the free hydrazine moiety in PLZ is crucial to producing the elevated levels of GABA, probably through inhibition of GABA-T. Despite the considerable increase in whole brain GABA levels in the PLZ-treated rats, there were no significant differences in GABAA or benzodiazepine receptor binding parameters (KD or Bmax) between the groups as measured using 3H-muscimol and 3H-flunitrazepam in radioligand binding assays.

Effects of age and of chronic antidepressant treatment on [3H]tryptamine and [3H]dihydroalprenolol binding to rat cortical membranes.

1. The effects of age and of chronic antidepressant treatment on [3H]tryptamine and [3H]dihydroalprenolol binding site density were measured in brain cortical membranes from male Sprague-Dawley rats. 2. The density but not the affinity of [3H]tryptamine binding sites was increased in 18-month-old rats relative to 3-month-old rats. Neither the density nor the affinity of [3H]dihydroalprenolol binding sites was affected by age. 3. Chronic administration (28 days s.c. via Alzet osmotic minipumps) of tricyclic antidepressant drugs (daily doses: imipramine.HCl, 30 mg kg-1; desipramine.HCl, 10 mg kg-1; clomipramine.HCl, 10 mg kg-1) resulted in decreases in [3H]dihydroalprenolol binding site density but no changes in [3H]tryptamine binding site density; no changes in affinity of either site were observed. 4. Chronic administration (s.c. via Alzet osmotic minipumps) of monoamine oxidase inhibitor antidepressant drugs (daily doses: tranylcypromine.HCl, 0.5 and 1.0 mg kg-1; phenelzine sulfate, 5 and 10 mg kg-1, each for 28 days; clorgyline.HCl, 1.0 mg kg-1; (-)-deprenyl.HCl, 1.0 mg kg-1, each for 14 days) resulted in decreases in [3H]tryptamine binding site density, without any effects on the affinity of this site. In addition, each of these monoamine oxidase inhibitors except (-)-deprenyl resulted in a decrease in [3H]dihydroalprenolol binding site density. No affinity changes were observed. 5. These data indicate that the [3H]tryptamine binding site exhibits physiological changes with aging and is differentially sensitive to the actions of tricyclic antidepressants and monoamine oxidase inhibitor antidepressants, respectively.

Effects of the antidepressant/antipanic drug phenelzine on GABA concentrations and GABA-transaminase activity in rat brain.

The effects of long-term (28-day) administration of several antidepressant/antipanic drugs [imipramine, desipramine, tranylcypromine and phenelzine (PLZ)] on gamma-aminobutyric acid-tranaminase (GABA-T) activity and GABA levels were investigated in rat frontal cortex. Of the drugs investigated, only PLZ inhibited GABA-T and elevated GABA levels. Additional short-term experiments were conducted with PLZ, and they demonstrated a dose-dependent inhibition of GABA-T in rat whole brain. Time-response studies on inhibition of GABA-T in whole brain demonstrated that at a dose of PLZ of 15 mg/kg i.p. inhibition of GABA-T remained relatively constant from 1 to 8 hr and that the enzyme was still inhibited by 23% at 24 hr after PLZ administration.

Beta-adrenoceptors and antidepressants: possible 2-phenylethylamine mediation of chronic phenelzine effects.

Effects of chronic administration of antidepressant drugs on beta-adrenoceptor function were assessed. Tricyclics (imipramine 30 mg/kg/day, desipramine 5 and 10 mg/kg/day) and monoamine oxidase inhibitors [(+/-)-tranylcypromine 1 mg/kg/day, phenelzine 5 and 10 mg/kg/day] were administered to Male Sprague-Dawley rats (n = 8), via Alzet 2ML2 osmotic minipumps for 28 days. Pumps were implanted subcutaneously in the interscapular region and replaced after 14 days. On days 21 and 22 motor-suppressant actions of the beta-adrenoceptor agonist salbutamol (3 mg/kg intraperitoneally [IP]) were assessed as a measure of beta-adrenergic receptor sensitivity. On day 28 the animals were killed and their brains used for measurement of drug levels and monoamine oxidase activity. Liver tissue was used to measure the trace amine 2-phenylethylamine. Each drug induced a decrease in the response to salbutamol. With phenelzine the decreased response to salbutamol was not observed at the lower dose. Differences in monoamine oxidase inhibition following phenelzine did not correspond to differential effects on functional beta-adrenergic sensitivity. Levels of 2-phenylethylamine, an endogenous amine that is also a metabolite of phenelzine, were significantly higher in the 10-mg/kg/day phenelzine group. These data suggest that 2-phenylethylamine may be one mediator of the chronic actions of phenelzine on beta-adrenoceptors.

Differential effects of antidepressants on GABAB and beta-adrenergic receptors in rat cerebral cortex.

The effects of chronic administration of antidepressant drugs on beta-adrenergic and gamma-amino-butyric acid (GABA)B receptors have been assessed with radioligand binding. Tricyclics [imipramine (IMI), 30 mg/kg/day, and desmethylimipramine (DMI), 10 mg/kg day] or monoamine oxidase inhibitors [(+/-)-tranylcypromine (TCP), 1 mg/kg/day, and phenelzine (PLZ), 10 mg/kg/day] were administered to male Sprague-Dawley rats by constant infusion via Alzet 2ML4 osmotic minipumps for 28 days. Pumps were implanted s.c. in the interscapular region. On day 28 the animals were killed and their brains removed; [3H]GABA binding to GABAB receptors was measured in frontal cortex and the remaining cortical tissue was used to measure [3H]dihydroalprenolol ([3H]DHA) binding to beta-adrenoceptors. All drugs tested induced a significant decrease in density (Bmax) of [3H]DHA binding, although no significant changes in affinity (Kd) were observed. [3H]GABA binding was not altered significantly by chronic antidepressant treatment. TCP-treated animals showed a tendency towards increased [3H]-GABA binding, but the differences did not reach statistical significance. No effects on Kd were observed. These data do not support the proposal that an increase in the total population of cortical GABAB receptors is a common effect of chronic antidepressant treatment.

Differential effects of chronic antidepressants in behavioural tests of beta-adrenergic and GABAB receptor function.

The effects of chronic administration of anti-depressant drugs (28 days SC via Alzet 2ML4 osmotic minipumps) on the functional sensitivity of beta-adrenergic and GABA receptors have been assessed. Phenelzine (10 mg/kg), tranylcypromine (1 mg/kg), imipramine (30 mg/kg) and desmethylimipramine (10 mg/kg) attenuated the motor-suppressant effects of salbutamol (3 mg/kg) observed at 21-22 days of drug administration. No changes in the motor-suppressant effects of the GABA prodrug progabide (50 mg/kg) or the GABAB agonist (+/-)-baclofen (5 mg/kg) were induced by these antidepressants. These findings extend and confirm previous reports of functional changes in beta-adrenergic receptors but not of GABAB receptors following chronic antidepressant treatment.

Stimulant-conditioned locomotion is not affected by blockade of D1 and/or D2 dopamine receptors during conditioning.

A series of experiments were conducted to investigate the role of dopamine (DA) D1 and D2 receptor subtypes in stimulant-conditioned locomotion in rats. Expt. 1 demonstrated that locomotion could be induced by a testing situation when that situation was previously paired with (+)-amphetamine (1.5 mg/kg, s.c.) or a D2 receptor selective agonist (PHNO, 15 or 30 micrograms/kg, s.c.), but not when the drug treatments were given 3 h after exposure to the situation. The selective D2 receptor antagonist, haloperidol (50 micrograms/kg, i.p.), and the D1 receptor antagonist, SCH 23390 (20 micrograms/kg, s.c.), blocked amphetamine-induced locomotion during the pairing process, but failed to block amphetamine-conditioned locomotion as assessed during a drug-free test in Expt. 2. This was true when the antagonists were given separately or together. The results of Expts. 3 and 4 showed that doses of the D1 (20 micrograms/kg, s.c.) and D2 antagonist (250 micrograms/kg, i.p.) that blocked the unconditioned locomotor effects of PHNO failed to block its conditioned locomotion. It is concluded that neither D1 nor D2 DA receptors are essential for the development of stimulant-conditioned locomotion.