Effects of quipazine and m-chlorophenylbiguanide (m-CPBG) on temporal differentiation: evidence for the involvement of 5-HT2A but not 5-HT3 receptors in interval timing behaviour
Tóm tắt
Temporal differentiation refers to animals’ ability to regulate their behaviour during an ongoing interval. Striatal dopaminergic mechanisms are purported to be involved in temporal differentiation, and recent evidence also implicates 5-hydroxytryptaminergic (5-HTergic) mechanisms, possibly mediated by 5-HT2A receptors. There is evidence that 5-HT3 receptors contribute to the regulation of dopamine release in the basal ganglia; however, it is not known whether 5-HT3 receptor stimulation can influence temporal differentiation. We examined the effects of a selective 5-HT3 receptor agonist m-CPBG, a mixed 5-HT2A/3 receptor agonist quipazine, and selective 5-HT3 and 5-HT2A receptor antagonists (MDL-72222 and ketanserin, respectively) on temporal differentiation in a free-operant psychophysical procedure. Twenty-four rats were trained to respond on two levers (A and B) under a free-operant psychophysical schedule, in which sucrose reinforcement (0.6 M, 50 μl) was provided intermittently for responding on A during the first half and on B during the second half of 50-s trials. Logistic psychometric functions were fitted to the relative response rate data [percent responding on B (%B) vs time from trial onset (t)], and quantitative indices of timing performance [T
50 (value of t corresponding to %B=50), Weber fraction, and mean time of switching from A to B, S
50] were derived. Quipazine (0.5, 1, and 2 mg kg−1) altered timing performance, dose-dependently reducing T
50 and S
50; m-CPBG (2.5, 5, and 10 mg kg−1) had no significant effect. The effect of quipazine was antagonized by ketanserin (2 mg kg−1), but not by MDL-72222 (1 mg kg−1). The present results provide no evidence for the involvement of 5-HT3 receptors in temporal differentiation and indicate that the effect of quipazine on performance was mediated by 5-HT2A receptor stimulation. The results are consistent with previous evidence for the involvement of 5-HT2A receptors in interval timing behaviour.
Tài liệu tham khảo
Al-Zharani SSA, Ho M-Y, Velazquez-Martinez DN, Lopez-Cabrera M, Bradshaw CM, Szabadi E (1996) Effect of the destruction of the 5-hydroxytryptaminergic pathways on behavioural timing and ‘switching’ in a free-operant psychophysical procedure. Psychopharmacology 127:346–352
Andrews N, File SE (1992) Are there changes in sensitivity to 5-HT3 receptor ligands following chronic diazepam treatment. Psychopharmacology 108:333–337
Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function. Neuropharmacology 38:1083–1152
Baxter G, Kennet GA, Blaney F, Blackburn T (1995) 5-HT2 receptor subtypes: a family reunited? Trends Pharmacol Sci 16:105–110
Bizo LA, White KG (1994a) Pacemaker rate and the behavioral theory of timing. J Exp Psychol, Anim Behav Processes 20:308–321
Bizo LA, White KG (1994b) The behavioral theory of timing: reinforcer rate determines pacemaker rate. J Exp Anal Behav 61:19–33
Blandina P, Goldfarb J, Craddock-Royal B, Green JP (1989) Release of endogenous dopamine by stimulation of 5-hydroxytryptamine3 receptors in rat striatum. J Pharm Exp Ther 251:803–809
Body S, Kheramin S, Mobini S, Velazquez-Martinez DN, Bradshaw CM, Szabadi E (2002) Antagonism by WAY-100635 of the effects of 8-OH-DPAT on performance on a free-operant timing schedule in intact and 5-HT depleted rats. Behav Pharmacol 13:603–614
Body S, Kheramin S, Ho M-Y, Miranda F, Bradshaw CM, Szabadi E (2003) Effects of a 5-HT2 receptor agonist, DOI (2,5-dimethoxy-4-iodoamphetamine), and antagonist, ketanserin, on the performance of rats on a free-operant timing schedule. Behav Pharmacol 14:599–607
Body S, Kheramin S, Ho M-Y, Miranda Herrera F, Bradshaw CM, Szanadi E (2004) Effects of fenfluramine on free-operant timing behaviour: evidence for involvement of 5-HT2A receptors. Psychopharmacology (in press)
Branch MN, Gollub LR (1974) A detailed analysis of the effects of d-amphetamine on behavior under fixed-interval schedules. J Exp Anal Behav 21:519–539
Carboni E, Acquas E, Frau R, DiChiara G (1989) Differential inhibitory effects of a 5-HT3 antagonist on drug-induced stimulation of dopamine release. Eur J Pharmacol 164:515–519
Catania AC, Reynolds GS (1968) A quantitative analysis of the responding maintained by interval schedules of reinforcement. J Exp Anal Behav 11:327–383
Cervo L, Pozzi L, Samanin R (1996) 5-HT3 receptor antagonists do no modify cocaine place conditioning or the rise in extracellular dopamine in the nucleus accumbens of rats. Pharmacol Biochem Behav 55:33–37
Chiang T-J, Al-Ruwaitea ASA, Ho M-Y, Bradshaw CM, Szabadi E (1998) The influence of “switching” on the psychometric function in the free-operant psychophysical procedure. Behav Processes 44:197–209
Chiang T-J, Al-Ruwaitea ASA, Ho M-Y, Bradshaw CM, Szabadi E (1999) Effect of central 5-hydroxytryptamine depletion on performance on the free-operant psychophysical procedure: facilitation of switching, but no effect on temporal differentiation of responding. Psychopharmacology 143:166–173
Chiang T-J, Al-Ruwaitea ASA, Mobini S, Ho M-Y, Bradshaw CM, Szabadi E (2000a) The effect of d-amphetamine on performance on two operant timing schedules. Psychopharmacology 150:170–184
Chiang T-J, Al-Ruwaitea ASA, Mobini S, Ho M-Y, Bradshaw CM, Szabadi E (2000b) Effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on performance on two operant timing schedules. Psychopharmacology 151:379–391
Costall B, Naylor RJ (1992) Anxiolytic potential of 5-HT3 receptor antagonists. Pharmacol Toxicol 70:157–162
DeDeurwaerdere P, Stinus L, Spampinato U (1998) Opposite changes of in vivo dopamine release in the rat nucleus accumbens and striatum that follows electrical stimulation of dorsal raphe nucleus: role of 5-HT3 receptors. J Neurosci 18:6528–6538
DiGiovanni G, DeDeurwaerdere P, Di Mascio M, Di Matteo V, Esposito E, Spampinato U (1999) Selective blockade of serotonin-2C/2B receptors enhances mesolimbic and mesostriatal dopaminergic function: a combined in vivo electrophysiological and microdialysis study. Neuroscience 91:587–597
Dukat M, Abdel-Rahman AA, Ismael AM, Ingher S, Teitler M, Gyermek L, Glennon RA (1996) Structure–activity relationships for the binding of arylpiperazines and arylbiguanides at 5-HT3 serotonin receptors. J Med Chem 39:4017–4026
Dukat M, Young R, Darmani NN, Ahmed B, Glennon RA (2000) The 5-HT3 agent N-(3-chlorophenyl)guanidine (MD-354) serves as a discriminative stimulus in rats and displays partial agonist in a shrew emesis assay. Psychopharmacology 150:200–207
Eguchi J, Inomata Y, Saito K-I (2001) The anxiolytic-like effect of MCI-225, a selective NA reuptake inhibitor with 5-HT3 receptor antagonism. Pharmacol Biochem Behav 68:677–683
Fozard JR (1984) MDL-72222: a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors. N S Arch Pharm 326:36–44
Gibbon J, Malpani C, Dale CL, Gallistel CR (1997) Toward a neurobiology of temporal cognition: advances and challenges. Curr Opin Neurobiol 7:170–184
Glennon RA, Ismaiel AEM, McCarthy BG, Peroutka SJ (1989) Binding of arylpiperazines to 5-HT3 serotonin receptors: results of a structure–affinity study. Eur J Pharmacol 168:387–392
Higgins GA, Joharchi N, Nguyen P, Sellers EM (1992) Effect of the 5-HT3 receptor antagonists, MDL72222 and ondansetron on morphine place conditioning. Psychopharmacology 106:315–320
Higgins GA, Joharchi N, Sellers EM (1993) Behavioral effects of the 5-hydroxytryptamine3 receptor agonists 1-phenylbiguanide and m-chlorophenylbiguanide in rats. J Pharmacol Exp Ther 264:1440–1449
Hinton SC, Meck WH (1997) How time flies: functional and neural mechanisms of interval timing. In: Bradshaw CM, Szabadi E (eds) Time and behaviour: psychological and neurobehavioural analyses. Elsevier, Amsterdam
Ho M-Y, Velazquez-Martinez DN, Bradshaw CM, Szabadi E (2002) 5-Hydroxytryptamine and interval timing behaviour. Pharmacol Biochem Behav 71:773–785
Hong E, Meneses A (1996) Systemic injection of p-chloroamphetamine eliminates the effect of the 5-HT3 compounds on learning. Pharmacol Biochem Behav 53:765–769
Hoyer D (1988) Functional correlates of 5-HT1 recognition sites. J Recept Res 8:59–81
Killeen P, Fetterman JG (1988) A behavioral theory of timing. Psychol Rev 95:274–295
Killeen P, Fetterman JG, Bizo LA (1997) Time’s causes. In: Bradshaw CM, Szabadi E (eds) Time and behaviour: psychological and neurobehavioural analyses. Elsevier, Amsterdam
Kilpatrick GJ, Butler A, Burridge J, Oxford AW (1990) 1-(m-Chlorophenyl)-biguanide, a potent high affinity 5-HT3 receptor agonist. Eur J Pharmacol 182:193–197
Lucas G, Spampinato U (2000) Role of striatal serotonin2A and serotonin2C receptor subtypes in the control of in vivo dopamine outflow in the rat striatum. J Neurochem 74:693–701
Machado A, Guilhardi P (2000) Shifts in the psychometric function and their implications for models of timing. J Exp Anal Behav 74:25–54
Maricq AV, Church RM (1983) The differential effects of haloperidol and metamphetamine on time estimation in the rat. Psychopharmacology 79:10–15
Maricq AV, Roberts S, Church RM (1981) Metamphetamine and time estimation. J Exp Psychol Anim Behav Processes 7:18–30
Matell MS, Meck WH (2000) Neuropsychological mechanisms of interval timing behaviour. BioEssays 22:94–103
Mazzola-Pomietto P, Aulakh CS, Murphy DL (1995) Temperature, food intake, and locomotor activity effects of a 5-HT3 receptor agonist and two 5-HT3 receptor antagonists in rats. Psychopharmacology 121:488–493
Meck WH (1986) Affinity for the dopamine D2 receptor predicts neuroleptic potency in decreasing the speed of an internal clock. Pharmacol Biochem Behav 25:1185–1189
Meck WH (1996) Neuropharmacology of timing and time perception. Cogn Brain Res 3:227–242
Nakagawa Y, Ishima T, Takashima T (1998) The 5-HT3 receptor agonist attenuates the action of antidepressants in the forced swim test in rats. Brain Res 786:189–193
Odum AL, Lieving LM, Schaal DW (2002) Effects of d-amphetamine in a temporal discrimination procedure: selective changes in timing or rate dependency? J Exp Anal Behav 78:195–214
Porras G, DeDeurwaerdere P, Moison D, Spampinato U (2003) Conditional involvement of striatal serotonin3 receptors in the control of in vivo dopamine outflow in the rat striatum. Eur J Neurosci 17:771–781
Sanger DJ, Blackman DE (1976) Rate-dependent effects of drugs: a review of the literature. Pharmacol Biochem Behav 4:73–83
Sharif NA, Wong EHF, Loury DN, Stefanich E, Michel AD, Eglen RM, Whiting RL (1990) Characteristics of 5-HT3 binding sites in NG108-15, NCB-20 neuroblastoma cells and rat cerebral cortex using [3H]-quipazine and [3H]-GR65630 binding. Br J Pharmacol 102:919–925
Smith RL, Gresch PJ, Barrett RJ, Sanders-Bush E (2002) Pharmacol Biochem Behav 72:77–85
Stubbs DA (1976) Scaling of stimulus duration by pigeons. J Exp Anal Behav 26:15–25
Wang RY, Ashby CR, Zhang JY (1996) Modulation of the A10 dopamine system: electrophysiological studies of the role of 5-HT3-like receptors. Behav Brain Res 73:7–10
Wolf A, Jackson A, Price T, Trevino A, Caldarolo-Pastuszka M, Uphouse L (1998) Attenuation of the lordosis-inhibiting effects of 8-OH-DPAT by TFMPP and quipazine. Brain Res 804:206–211
Wolff MC, Leander JD (2000) A comparison of the behavioural effects of 5-HT2A and 5-HT2C receptor agonists in the pigeon. Behav Pharmacol 11:355–364
Zazpe A, Artaiz I, Del Rio J (1994) Role of 5-HT3 receptors in basal and K+-evoked dopamine release from rat olfactory tubercle and striatal slices. Br J Pharmacol 113:968–972