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The tricyclic antidepressants, including desipramine (DMI), are no better than placebo in treating childhood and adolescent depression, but are effective in adult depression. Animal studies comparing the effects of DMI in juveniles and adults are complicated by age-related variations in elimination rates. Thus, different dosing regiments are needed to achieve similar brain drug levels in juvenile and adult rats. We compared the half-life of DMI as well as the brain and serum concentrations of DMI and its active metabolite desmethyldesipramine in juvenile and adult rats after various drug administration paradigms. After acute i.p. administration DMI is eliminated from the brain more slowly in postnatal day (PND) 21 and 28 rats as compared to adults. After chronic i.p. administration (for 4-5 days between PND 9 and 28), lower doses of DMI are needed with juvenile rats to obtain the same brain DMI concentrations as adults. By contrast, two weeks of continuous drug delivery (minipump) to PND 21-35 and adult rats result in similar brain DMI concentrations. Thus, the pharmacokinetic properties of DMI varies with the age of the animal and dosing of DMI and needs to be carefully adjusted in order to have appropriate brain levels of the drug.

Norepinephrine and epinephrine are catecholamine messengers that play important roles in the regulation of diverse physiological systems by acting through adrenergic receptors. The study of these biogenic amines has played an important historical role in the development of contemporary neuropharmacology. The study of the synthesis and metabolism of these compounds has provided important drug targets as has the study of the norepinephrine transporter. Adrenergic receptors are divided into three major types: α 1 , α 2 and β. Each of these major types has three or more subtypes. Many important therapeutic drugs act on this array of nine or more receptors. Genetic variations in all of the enzymes, transporters and receptors involved with norepinephrine and epinephrine are receiving intense study at the present time.

The expression of brain-derived neurotrophic factor (BDNF) mRNA and protein and its primary receptor, TrkB mRNA shows circadian oscillations in adult rats; however it has been unclear if juvenile rats also display a similar pattern in circadian oscillations. We determined the levels of BDNF and TrkB mRNA and of BDNF protein at four separate time points during a 24 hperiod in the hippocampus and frontal cortex. The expression of BDNF and TrkB undergoes diurnal oscillation in adult and postnatal day 21 rats, but no significant variation is present in postnatal day 13 rats. Antidepressant drug treatment also is known to influence BDNF and TrkB levels. However, the reported effects of antidepressant drug treatment on BDNF and TrkB are highly variable and may be influenced by multiple factors, including detection method, class of antidepressant drug, and length of administration. BDNF mRNA levels were decreased significantly in the hippocampus after acute desipramine (a tricyclic antidepressant) treatment compared to control. BDNF mRNA and protein levels, as well as TrkB mRNA levels, were unchanged in adult rats after subchronic and chronic treatment with either desipramine or escitalopram (a selective serotonin reuptake inhibitor) and treatment consistent with several reports in the literature. This study defines several important factors that must be taken into account when comparing BDNF and TrkB levels both within and among studies.