ABSTRACT
The effects of selective NK-1, NK-2 and NK-3 tachykinin agonists in midbrain dopamine cell containing regions were investigated in the rat. The NK-3 agonist senktide induced locomotion, rearing and sniffing following infusion into the substantia nigra pars compacta, and to a lesser extent in the ventral tegmental area. These behavioural responses were not seen following infusion of the selective NK-1 agonist [Sar9,Met (O2)11]SP or the NK-2 agonist [N1e10]NKA4-10. In contrast, grooming was induced only by the NK-1 agonist administered into the substantia nigra. Yawning, chewing mouth movements and wet dog shakes were all seen following infusion of senktide into the ventral tegmental area. These findings suggest that (i) dopamine-mediated behavioural responses seen following tachykinin administration into the midbrain are dependent upon stimulation of NK-3 tachykinin receptors, (ii) tachykinin-induced grooming is mediated by stimulation of NK-1 receptors and (iii) some of the previously described 5-HT mediated behaviours seen following administration of NK-3 tachykinin agonists are probably generated by stimulation of 5-HT cell bodies in the ventral tegmental area.
Subject(s)
Behavior, Animal/drug effects , Dopamine/physiology , Mesencephalon/drug effects , Receptors, Neurotransmitter/drug effects , Tachykinins , Animals , Grooming/drug effects , Locomotion/drug effects , Male , Movement/drug effects , Rats , Rats, Sprague-Dawley , Receptors, TachykininABSTRACT
The effects of intracerebroventricular neurotensin and the neurotensin analogues neuromedin N and [D-Trp 11]neurotensin on the behavioural responses to chronic neuroleptic administration were investigated in the rat. Chronic (18 weeks) administration of a low dose (12.5 mg/kg, i.m., every 3 weeks) of fluphenazine decanoate alone failed to elicit the vacuous chewing mouth movements (VCMs) which have previously been reported following higher doses of this drug, but VCMs were seen in neuroleptic-treated animals following the additional administration of neurotensin. A higher dose of fluphenazine (25 mg/kg, i.m., every 3 weeks) greatly increased the VCM response, and this potentiation was suppressed to control levels by [D-Trp11]neurotensin, but unaffected by neuromedin N. These findings suggest that alterations in neurotensin may contribute to the deleterious extrapyramidal effects of long-term neuroleptic administration, and that [D-Trp11]neurotensin may attenuate these effects by blockade of neurotensin receptors within the central nervous system.
