The 5 -HT3 receptor antagonists, granisetron and ondansetron, do not affect cocaine-induced shifts in intra-cranial self-stimulation thresholds

Abstract

The effects of the 5-HT( 3) receptor antagonists, granisetron and ondansetron, were investigated on behaviour maintained by intracranial self-stimulation (ICSS). Rats, implanted with bipolar electrodes in the lateral hypothalamus, were trained to lever press on a continuous reinforcement schedule for positively reinforcing trains of electrical stimulation. The frequency at which responding reached 50% of maximum (M50) and the maximum rate of responding (asymptote) were used to measure drug effects. Granisetron (0.01-0.1 mg/kg i.p ) and ondansetron (0.03-0.3 mg/kg i.p ) had no effect on either parameter. In contrast, cocaine (20 mg/kg i.p ) potentiated rewarded responding, reducing M50 values, but neither granisetron (0.01-3.0 mg/kg i.p ) nor ondansetron (0.03-0.3 mg/kg i.p ) blocked this effect. Neither did granisetron (0.1-10.0 mg/kg i.p ) alter the effect of lower doses of cocaine (10 mg/kg i.p.). These data suggest that 5 -HT( 3) receptors do not play a significant role in mediating responding maintained by ICSS in the rat through hypothalamic electrodes. Neither do they modulate cocaine-induced potentiation of the behaviour.

The effects of dopamine D 3 /D 2 receptor agonists on intracranial self stimulation in the rat

“…Dopamine receptor antagonists such as haloperidol, pimozide and spiroperidol decrease ICSS responding maintained by electrodes implanted in the lateral hypothalamus (Wauquier and Niemegers 1972;Rolls et al 1974;Phillips et al 1975). Cocaine and amphetamine, which increase synaptic dopamine levels, increase the rate of ICSS responding and induce a leftward shift in frequencyresponse curves (Gallistel and Karras 1984;Hatcher et al 1995). This shift is thought to reßect the rewarding properties of these drugs, and similar potentiation has been reported for the dopamine receptor agonists quinpirole (Nakajima et al1993;Ranaldi and Beninger 1994a,b), apomorphine (Fourriezos and Francis 1992) and bromocriptine (Knapp and Kornetsky 1994).…”

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

“…ICSS is generally not affected or only depressed by systemically administered agonists and/or antagonists for 5HT 1 receptors (Harrison et al, 1999;Harrison and Markou, 2001), 5HT 2 receptors (Benaliouad et al, 2007;Hayes et al, 2009;Katsidoni et al, 2011), 5HT 3 receptors (Greenshaw, 1993;Hatcher et al, 1995), and 5HT 4 receptors (Reavill et al, 1998) (see Hayes and Greenshaw, 2011 for review). An exception is that low doses of the 5HT 1A agonist 8-OH-DPAT may facilitate ICSS (Harrison and Markou, 2001).…”