Electrophysiological evidence for locus coeruleus norepinephrine autoreceptor subsensitivity following subchronic administration of D-amphetamine.

The effect produced by subchronic administration of D-amphetamine (D-AMP) on the sensitivity of norepinephrine (NE) autoreceptors in the rat locus coeruleus (LC) was studied by means of single unit recording and microiontophoretic techniques. Twice daily i.p. administration of 5 mg/kg D-AMP for one week markedly reduced the ability of i.v. D-AMP and microiontophoretic application of clonidine to suppress the firing of LC NE neurons, suggesting strongly that NE autoreceptors became subsensitive. In addition, the firing pattern of NE neurons became 'disorganized' following subchronic AMP treatment.