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Depletion of brain serotonin following intra-raphe injections of 5,7-dihydroxytryptamine does not alter d-amphetamine self-administration across different schedule and access conditions.
Psychopharmacology (Berl). 1999 Sep; 146(2):185-93.P

Abstract

OBJECTIVES

These experiments investigated the effects of selective serotonin (5-HT) depletion on intravenous self-administration of d-amphetamine.

METHODS

Depletion of brain 5-HT levels was induced by injecting the serotonergic neurotoxin 5,7-dihydroxytryptamine (5, 7-DHT) into the dorsal and median raphe nuclei. Rats were then trained to self-administer d-amphetamine according to various schedule and access conditions via chronically indwelling intravenous catheters.

RESULTS

Large reductions of brain 5-HT did not alter responding for a training dose of 120 microgram/kg d-amphetamine delivered according to a fixed ratio 1 schedule during 3-h sessions. When the dose of d-amphetamine was altered (0, 3.75, 7. 5, 15, 30, 60 microgram/kg per infusion) a characteristic inverted U-shaped dose response function was obtained. The 5-HT depleted rats showed increased responding for the lower doses of d-amphetamine, with a large significant increase in responding for the 7.5 microgram/kg dose. In these same rats, the suppressive effect of 10 mg/kg fluoxetine on d-amphetamine (60 microgram/kg) self-administration was prevented. The 5,7-DHT lesion also did not alter responding for d-amphetamine (120 microgram/kg) in longer (8 h) daily access sessions. Responding for d-amphetamine delivered on a progressive ratio schedule, in which response requirements increased for each successive infusion of d-amphetamine, was also determined in 5-HT depleted rats. The number of d-amphetamine infusions was not different from the number of infusions earned by sham-lesioned rats across a range of doses of d-amphetamine (7.5-60 microgram/kg). In a final experiment, spontaneous acquisition of self-administration of low doses of d-amphetamine (10 and 30 microgram/kg) was measured in 5-HT depleted and control rats. Again, self-administration behaviour in the 5-HT depleted rats did not differ from controls.

CONCLUSIONS

These results provide no evidence that reducing 5-HT function alters the primary reinforcing effects of self-administered amphetamine. The increase in self-administration of a low dose of amphetamine observed in experiment 1 probably involves some other process such as increased resistance to extinction.

Authors+Show Affiliations

Departments of Psychiatry, University of Toronto, Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, Ontario, Canada M5T 1R8. fletcher@psych.toronto.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10525754

Citation

Fletcher, P J., et al. "Depletion of Brain Serotonin Following Intra-raphe Injections of 5,7-dihydroxytryptamine Does Not Alter D-amphetamine Self-administration Across Different Schedule and Access Conditions." Psychopharmacology, vol. 146, no. 2, 1999, pp. 185-93.
Fletcher PJ, Korth KM, Chambers JW. Depletion of brain serotonin following intra-raphe injections of 5,7-dihydroxytryptamine does not alter d-amphetamine self-administration across different schedule and access conditions. Psychopharmacology (Berl). 1999;146(2):185-93.
Fletcher, P. J., Korth, K. M., & Chambers, J. W. (1999). Depletion of brain serotonin following intra-raphe injections of 5,7-dihydroxytryptamine does not alter d-amphetamine self-administration across different schedule and access conditions. Psychopharmacology, 146(2), 185-93.
Fletcher PJ, Korth KM, Chambers JW. Depletion of Brain Serotonin Following Intra-raphe Injections of 5,7-dihydroxytryptamine Does Not Alter D-amphetamine Self-administration Across Different Schedule and Access Conditions. Psychopharmacology (Berl). 1999;146(2):185-93. PubMed PMID: 10525754.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Depletion of brain serotonin following intra-raphe injections of 5,7-dihydroxytryptamine does not alter d-amphetamine self-administration across different schedule and access conditions. AU - Fletcher,P J, AU - Korth,K M, AU - Chambers,J W, PY - 1999/10/20/pubmed PY - 1999/10/20/medline PY - 1999/10/20/entrez SP - 185 EP - 93 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 146 IS - 2 N2 - OBJECTIVES: These experiments investigated the effects of selective serotonin (5-HT) depletion on intravenous self-administration of d-amphetamine. METHODS: Depletion of brain 5-HT levels was induced by injecting the serotonergic neurotoxin 5,7-dihydroxytryptamine (5, 7-DHT) into the dorsal and median raphe nuclei. Rats were then trained to self-administer d-amphetamine according to various schedule and access conditions via chronically indwelling intravenous catheters. RESULTS: Large reductions of brain 5-HT did not alter responding for a training dose of 120 microgram/kg d-amphetamine delivered according to a fixed ratio 1 schedule during 3-h sessions. When the dose of d-amphetamine was altered (0, 3.75, 7. 5, 15, 30, 60 microgram/kg per infusion) a characteristic inverted U-shaped dose response function was obtained. The 5-HT depleted rats showed increased responding for the lower doses of d-amphetamine, with a large significant increase in responding for the 7.5 microgram/kg dose. In these same rats, the suppressive effect of 10 mg/kg fluoxetine on d-amphetamine (60 microgram/kg) self-administration was prevented. The 5,7-DHT lesion also did not alter responding for d-amphetamine (120 microgram/kg) in longer (8 h) daily access sessions. Responding for d-amphetamine delivered on a progressive ratio schedule, in which response requirements increased for each successive infusion of d-amphetamine, was also determined in 5-HT depleted rats. The number of d-amphetamine infusions was not different from the number of infusions earned by sham-lesioned rats across a range of doses of d-amphetamine (7.5-60 microgram/kg). In a final experiment, spontaneous acquisition of self-administration of low doses of d-amphetamine (10 and 30 microgram/kg) was measured in 5-HT depleted and control rats. Again, self-administration behaviour in the 5-HT depleted rats did not differ from controls. CONCLUSIONS: These results provide no evidence that reducing 5-HT function alters the primary reinforcing effects of self-administered amphetamine. The increase in self-administration of a low dose of amphetamine observed in experiment 1 probably involves some other process such as increased resistance to extinction. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/10525754/Depletion_of_brain_serotonin_following_intra_raphe_injections_of_57_dihydroxytryptamine_does_not_alter_d_amphetamine_self_administration_across_different_schedule_and_access_conditions_ L2 - https://dx.doi.org/10.1007/s002130051105 DB - PRIME DP - Unbound Medicine ER -