GABAergic mechanisms in the nucleus accumbens septi regulating rat motor activity: the effect of chronic treatment with desipramine.
The influence of chronic treatment with desipramine upon GABAergic mechanisms within the nucleus accumbens septi (NAS) affecting rat motor behavior was studied in the automatic open fields. It was shown that intra-accumbens injections of picrotoxin on one hand and muscimol and baclofen on the other, produced dose-dependent increase or decrease in rat motility, respectively. Locomotor stimulation usually observed after picrotoxin did not occur in rats given local injections of a solution containing both picrotoxin and GABA A receptor agonist muscimol. Muscimol (130 ng as a pure compound) blocked also hypermotility produced by intra-accumbens administration of dopamine releasing drug d-amphetamine (10 micrograms). This part of the experiment was summarized as indicating that both GABA A and GABA B receptor-related mechanisms, which are under negative control of dopaminergic neurons in the NAS, play an important role in regulating behavior in the rat. In the second part of the experiment it was observed that chronic treatment of rats with desipramine (DMI) (10 mg/kg, PO, twice daily for 21 days, rats were tested 24 hr after the last dose of the drug) significantly attenuated or blocked the inhibitory effect on locomotion of both baclofen and muscimol. The stimulatory influence of picrotoxin seemed also to be diminished, but it still attained the level of accepted statistical significance. On the basis of these and other data it is concluded that observed changes in the effects of GABAergic agonists in DMI-treated rats are probably due to an enhancement of local dopaminergic mechanisms, thus leading to the potentiation of a negative interaction between dopaminergic and GABAergic mechanisms within the NAS.(ABSTRACT TRUNCATED AT 250 WORDS)
Płaznik
A
A
Department of Pharmacology and Physiology, Nervous System Institute of Psychiatry and Neurology, Warsaw, Poland.
Stefański
R
R
Kostowski
W
W
D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D012686:Septal Nuclei / Q000187:drug effects*
D001418:Baclofen; D003891:Desipramine; D009118:Muscimol; D010852:Picrotoxin; D011963:Receptors, GABA-A