Modulation of cocaine-induced locomotor activity, rears and head bobs by application of WAY100635 into the dorsal and median raphe nuclei of the rat

Abstract

The present study investigated the role of somatodendritic 5-HT1A autoreceptors located in the dorsal and median raphe nuclei on the stimulant effect of cocaine on locomotor activity, rears and head bobs in female Glaxo Wistar rats. Cocaine was administered at a submaximal dose of 15 mg/kg i.p. to enable either a potentiation or attenuation to be observed. The selective 5-HT1A antagonist WAY100635 (0.21 ng or 21 ng) or saline was microinjected in the dorsal or median raphe nuclei followed by the peripheral administration of cocaine 60 min later. WAY 100635 microinjected in the dorsal or median raphe nuclei did not consistently alter the locomotor activity and the number of rears of saline-treated animals. Microinjection of WAY100635 in the dorsal raphe nucleus potentiated cocaine-induced locomotor activity and the number of head bobs. The number of rears induced by cocaine was not significantly altered by WAY100635 microinjected in the dorsal raphe nucleus. In contrast, microinjection of WAY100635 in the median raphe nucleus did not alter the stimulant effect of cocaine on locomotor activity, rears or head bobs. It may be suggested from these results that stimulation of somatodendritic 5-HT1A autoreceptors located in the dorsal raphe nucleus mediates an inhibitory effect on cocaine-induced locomotor activity and head bobs, whereas somatodendritic 5-HT1A autoreceptors in the median raphe nucleus are not involved in the inhibitory role of 5-HT on the stimulant effect of cocaine on locomotor activity and head bobs. A differential involvement of the midbrain raphe nuclei may exist controlling the stimulant effect of cocaine on locomotor activity and head bobs.

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

“…The main source of 5-HT in the mPFC is the dorsal raphé nucleus (Vertes 1991). Therefore, a role for the mPFC in cocaine-induced hyperactivity is consistent with the finding, that intradorsal raphé injections of a 5-HT1A antagonist or agonist, modulate this behavior (Herges and Taylor 1999;Szumlinski et al 2004). Furthermore, a modulatory effect of prefrontal 5-HT receptors was suggested by Filip and Cunningham (2003), who found reduced cocaine-stimulated locomotion following infusion of a 5-HT2C agonist into the mPFC.…”

Insulin Modulates Cocaine-Sensitive Monoamine Transporter Function and Impulsive Behavior

“…Two animals died during surgery, and three animals were excluded due to cannula misplacement (resulting group sizes: vehicle ϩ saline, n ϭ 8; vehicle ϩ cocaine, n ϭ 7; insulin ϩ saline, n ϭ 6, and insulin ϩ cocaine, n ϭ 6). Unlike intraperitoneal administration of 5 mg/kg cocaine (data not shown) (Herges and Taylor, 1999), a dose of 10 mg/kg caused a consistent hyperlocomotor response (Fig. 7) (treatment: F (3,23) ϭ 10.80, p Ͻ 0.001; time ϫ treatment: F (33,253) ϭ 7.15, p Ͻ 0.001).…”

Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats

“…The mechanism underlying this 5-HT dampening is not understood. As activation of inhibitory somatodendritic 5-HT 1A receptors reduces the firing rate of raphe neurons and subsequently 5-HT and DA release in terminal regions (Yoshimoto and McBride 1992;Herges and Taylor 1999;Andrews et al 2005), desensitization of somatodendritic 5-HT 1A receptors in SERT −/− models may mediate the reduced 5-HT dampening and cocaine supersensitivity. On the other hand, there are also indications that somatodendritic 5-HT 1A receptors facilitate psychostimulant addiction-related behaviors and that postsynaptic 5-HT 1A receptors predominantly inhibit psychostimulant-induced locomotor activity (Müller et al 2007).…”