Chronic desipramine enhances amphetamine-induced increases in interstitial concentrations of dopamine in the nucleus accumbens.
There is accumulating evidence that some antidepressant treatments can increase the functional output of the meso-accumbens dopaminergic system. For example, chronic administration of tricyclic antidepressant drugs such as imipramine and desipramine (DMI) enhances the locomotor stimulant effects of d-amphetamine. Subsensitivity of inhibitory dopamine (DA) autoreceptors and supersensitivity of postsynaptic DA receptor mechanisms are among the mechanisms that have been suggested to underlie these observations. The present experiments investigated the effects of acute and chronic DMI treatment on interstitial DA concentrations in the nucleus accumbens and striatum using in vivo microdialysis in awake freely moving rats (48 h following implantation of a microdialysis probe). Neither acute (5 mg/kg b.i.d. for 2 days followed by 72 h withdrawal) nor chronic (5 mg/kg b.i.d. for 21 days followed by 72 h withdrawal) DMI influenced the ability of apomorphine (25 micrograms/kg s.c.) to decrease extracellular concentrations of DA or its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens. In contrast, d-amphetamine (1.5 mg/kg s.c.)-induced increases in extracellular DA were significantly enhanced in the nucleus accumbens of the chronic but not the acute DMI group. This effect was at least partially regionally selective, as significant effects were not observed in the striatum. In accordance with previous reports, the locomotor stimulant effects of d-amphetamine were also enhanced in the chronic DMI groups. DMI itself failed to alter the interstitial concentrations of DA and its metabolites in the nucleus accumbens of the control and chronic DMI groups. These results provide in vivo neurochemical confirmation that chronically administered DMI does not produce DA autoreceptor subsensitivity. They also demonstrate that chronic DMI-induced increases in the locomotor stimulant effects of d-amphetamine are accompanied by a selective potentiation of the effects of this stimulant on interstitial DA concentrations in the nucleus accumbens.
Nomikos
G G
GG
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Damsma
G
G
Wenkstern
D
D
Fibiger
H C
HC
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000929:Antidepressive Agents, Tricyclic; D000661:Amphetamine; D003891:Desipramine; D004298:Dopamine