Microinjection of cocaine into the nucleus accumbens elicits locomotor activation in the rat

Abstract

Cocaine is believed to exert its psychostimulant effects through activation of the mesocorticolimbic system. Although the nucleus accumbens, in particular, has been hypothesized as the site of action of cocaine's stimulating effects, there is no direct evidence that microinjection of cocaine into this region produces behavioral activation. The present experiments investigated the locomotor response to microinjection of cocaine (0, 10, 30, 100 micrograms/0.5 microliter) into the nucleus accumbens in rats. Cocaine elicited a pronounced, dose-dependent motor activation of approximately 60 min duration. This stimulant effect was blocked by prior administration of a dopamine (DA) receptor antagonist, cis-flupenthixol. The response to cocaine was differentiated from nucleus accumbens microinjections of procaine and lidocaine, compounds that have potent local anesthetic effects but little affinity for the dopamine-uptake site. Neither procaine nor lidocaine (0, 10, 30, 100 micrograms/0.5 microliter) had any overall effect, although activity was somewhat decreased in the initial part of the test session and increased at the end, relative to control activity. Cocaine injected into the anterior dorsal or ventrolateral striatum (100 micrograms) also increased motor activity; procaine and lidocaine had no effect. Cocaine injected into the ventrolateral striatum significantly increased stereotypy. The amplitude of motor activation following cocaine injection into nucleus accumbens was much greater than that elicited at the other striatal sites. Further, observation of the time course of motor activation following cocaine injection into the anterior dorsal and ventrolateral striatum suggested that the motor effect was due to diffusion, most likely to the nucleus accumbens.(ABSTRACT TRUNCATED AT 250 WORDS)

D1 dopamine receptor: A putative neurochemical and behavioral link to cocaine action

“…Dopamine is important in modulating both motivational and behavioral reactivity (Delfs et al, 1990;Salamone, 1996) and as described, cocaine potentiates dopaminergic neurotransmission within the mesocorticolimbic dopamine circuit. This circuit has been directly implicated not only in reinforcement and reward, but also in the control of locomotor activity (Pijnenburg et al, 1976).…”

“…This circuit has been directly implicated not only in reinforcement and reward, but also in the control of locomotor activity (Pijnenburg et al, 1976). Therefore, it is maintained that the ability of cocaine to accentuate locomotor behavior in animals is dependent upon its mechanism of indirectly potentiating dopaminergic function within mesolimbic areas such as the nucleus accumbens (Kelly et al, 1975;Kelly and Iversen, 1976;Delfs et al, 1990). Furthermore, the physiological actions of dopamine are mediated by D 1 and D 2 dopamine receptors, which have been implicated as speci®c targets in cocaine-induced locomotion.…”

Involvement of 5‐HT3 receptors in the nucleus accumbens in the potentiation of cocaine‐induced behaviours in the rat

“…In agreement with a facilitatory role of 5-HT 3 receptors on locomotor activity induced by psychomotor stimulants is the reported observation, that the increased locomotion following intra-NAc administration of amphetamine was antagonized by ondansetron, however, the 5-HT 3 receptor antagonist failed to reduce locomotor activity elicited by peripherally administered amphetamine (Costall et al, 1987). The reported failure of ondansetron on amphetamine's stimulatory properties on behaviours following peripheral administration was attributed to its additional interaction with the striatum (Costall et al, 1987), a dopaminergic brain region which is associated with stereotypic behaviours elicited by psychomotor stimulants (Kelly et al, 1975;Delfs et al, 1990). In the present study, the ability of ondansetron microinjected into the core of the NAc to reduce locomotor and head bobbing activities elicited by peripherally administered cocaine may suggest a preferential involvement of this brain region in these exploratory behaviours induced by cocaine.…”

“…It is believed that the dopaminergic nerve terminals in the NAc with cell bodies located in the ventral tegmental area (VTA) are crucially involved in cocaine's stimulatory e ect on locomotor activity in rats (Kelly & Iversen, 1976;Delfs et al, 1990;Kaddis et al, 1993;Neisewander et al, 1998). Besides cocaine's neurochemical e ects on the dopaminergic mesoaccumbens circuit (Bradberry & Roth, 1989;Carboni et al, 1989;Chen & Reith, 1994), the psychomotor stimulant also interacts with the serotoninergic neurotransmitter system (for review see Cunningham et al, 1996), which may contribute to its overall behavioural pro®le.…”

“…Due to the strong implication of the NAc in cocaine's locomotor stimulatory e ect (Kelly & Iversen, 1976;Delfs et al, 1990;Kaddis et al, 1993;Neisewander et al, 1998), this dopaminergic brain region appeared to be a suitable target site to investigate¯uoxetine's modulatory e ect after microinjection into the NAc. In addition, the potential involvement of 5-HT 3 receptors in cocaine's as well as¯uoxetine's e ects was investigated by intra-NAc administration of ondansetron.…”