Neurokinin₃ receptor activation potentiates the psychomotor and nucleus accumbens dopamine response to cocaine, but not its place conditioning effects

Abstract

Neurokinin(3) receptors (NK(3)-Rs) have been implicated in psychomotor activity and reinforcement mechanisms. Recently, we showed that NK(3)-R antagonism blocked the psychostimulant properties of cocaine both in rats and in primates. Here, using in vivo microdialysis in the nucleus accumbens (NAc) of freely moving rats, we investigated the effect of the NK(3)-R agonist senktide (0.2 and 0.4 mg/kg s.c.) on the cocaine-evoked increase in dopamine. Cocaine (10 mg/kg i.p.) increased dopamine levels to 404 and 480% of baseline in the core and shell of the NAc, respectively. Pretreatment with senktide at a dose of 0.2 mg/kg potentiated this effect to 666 (core) and 869% (shell) of baseline, without having any effect on dopamine when given alone. Behavioural measurements revealed that 0.2 mg/kg senktide also potentiated the cocaine-induced increase in horizontal and vertical activity. Senktide alone induced a short-lasting increase in activity that was not accompanied by any alterations of the neurochemical parameters. In conditioned place preference (CPP) experiments, senktide pretreatment did not alter CPP induced by cocaine (5 and 10 mg/kg i.p.), and had no effect when given alone. Likewise, cocaine-conditioned locomotor activity was not affected by the NK(3)-R agonist. However, as in the microdialysis studies, cocaine-induced (5 and 10 mg/kg i.p.) hyperactivity was potentiated by senktide, and there was evidence for a facilitation of sensitization to the hyperlocomotor effects of cocaine by senktide. These data provide evidence that NK(3)-Rs are involved in the control of the hyperlocomotor and NAc DA response to cocaine, but not in cocaine-induced CPP.

Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines

“…In contrast, both the low and high dietary sodium exposure in the Wistar strain potentiated the adult offsprings' behavioral responses to amphetamine. The susceptibility of different substrains to dietary sodium manipulation may be tied to differences in the expression of receptors, such as the tachykinins, in brain regions that mediate the psychomotor stimulant and reinforcing properties of amphetamine and sodium solutions (27,32). These results add to the literature identifying strain differences in salt intake, responses to stress, and psychomotor stimulant sensitivity (2,5,35,43,54).…”

Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism

“…senktide treatment, but a sensitization for the arousal-enhancing effects of cocaine (32). Subchronic treatment in adult rats had neither aversive nor appetitive effects on its own and did not impair the action of other reinforcers (33). In the present study we observed neither hyperlocomotion nor other behavioral effects that had been reported after, e.g., i.c.v.…”

“…As such, NK3-R agonists may also serve to prevent aging-associated decline in cholinergic function. However, although adult rats and nonhuman primates appear to tolerate NK3-R agonists well after subchronic treatment (32,33), little is known about tolerance in the aged organism. Recent animal studies suggest that the use of NK3-R agonists may be limited in Parkinsons's disease (39).…”

Role of medial prefrontal, entorhinal, and occipital 5-HT in cocaine-induced place preference and hyperlocomotion: evidence for multiple dissociations

“…Illumination was provided indirectly by a 100-W light bulb in one of the upper corners of the light-and soundattenuating room, in which the apparatus was setup (resulting in an illumination level of 1.5 lx near the walls, 2.5 lx in the middle of the apparatus). A camera, connected to a VCR and a PC, was installed above the open field (Jocham et al 2006(Jocham et al , 2007. Habituation learning and LIA were investigated in an open field (40×40×39 cm) of a TruScan system (Coulbourn Instruments, Allentown, PA, USA), which was situated in a sound and light isolated chamber (110×70×70 cm).…”