Stephen J Kohut1,2, Jack Bergman3,4. 1. Preclinical Pharmacology Laboratory, McLean Hospital, 115 Mill Street, Belmont, MA, USA. skohut@mclean.harvard.edu. 2. Department of Psychiatry, Harvard Medical School, Belmont, MA, USA. skohut@mclean.harvard.edu. 3. Preclinical Pharmacology Laboratory, McLean Hospital, 115 Mill Street, Belmont, MA, USA. 4. Department of Psychiatry, Harvard Medical School, Belmont, MA, USA.
Abstract
RATIONALE: Despite the high prevalence of nicotine use in humans, robust nicotine self-administration has been difficult to demonstrate in laboratory animals. OBJECTIVES: A parametric analysis of nicotine self-administration was conducted to study its reinforcing effects in nonhuman primates. METHODS: Adult rhesus macaques (N = 6) self-administered intravenous (IV) nicotine (0.001-0.1 mg/kg) under a fixed-ratio (FR)1 schedule of reinforcement during daily 90-min sessions. Next, the demand function relating drug intake and response cost was determined by increasing the FR across sessions during the availability of each of several unit doses of nicotine (0.0032-0.032 mg/kg/inj). The reinforcing effects of 0.01 mg/kg/inj cocaine and 1 g banana-flavored food pellets were also determined under similar testing conditions. Finally, the nicotine demand function was re-determined after approximately 8 months of daily IV nicotine self-administration. RESULTS: IV nicotine self-administration followed an inverted U-shaped pattern, with the peak number of injections maintained by 0.0032 mg/kg/inj. Self-administration of each reinforcer (food pellets, IV cocaine, and IV nicotine) decreased as FR size increased. Application of the exponential model of demand showed that demand elasticity for nicotine was (1) dose-dependent and lowest for 0.0032 mg/kg/inj; (2) for 0.0032 mg/kg/inj, similar to that of food pellets and significantly higher than cocaine; and (3) decreased after 8 months of daily nicotine self-administration. CONCLUSIONS: These data show that, though high levels of nicotine self-administration can be achieved under simple FR schedules in nonhuman primates, its reinforcing effectiveness is dose-related but limited and may increase over time.
RATIONALE: Despite the high prevalence of nicotine use in humans, robust nicotine self-administration has been difficult to demonstrate in laboratory animals. OBJECTIVES: A parametric analysis of nicotine self-administration was conducted to study its reinforcing effects in nonhuman primates. METHODS: Adult rhesus macaques (N = 6) self-administered intravenous (IV) nicotine (0.001-0.1 mg/kg) under a fixed-ratio (FR)1 schedule of reinforcement during daily 90-min sessions. Next, the demand function relating drug intake and response cost was determined by increasing the FR across sessions during the availability of each of several unit doses of nicotine (0.0032-0.032 mg/kg/inj). The reinforcing effects of 0.01 mg/kg/inj cocaine and 1 g banana-flavored food pellets were also determined under similar testing conditions. Finally, the nicotine demand function was re-determined after approximately 8 months of daily IV nicotine self-administration. RESULTS: IV nicotine self-administration followed an inverted U-shaped pattern, with the peak number of injections maintained by 0.0032 mg/kg/inj. Self-administration of each reinforcer (food pellets, IV cocaine, and IV nicotine) decreased as FR size increased. Application of the exponential model of demand showed that demand elasticity for nicotine was (1) dose-dependent and lowest for 0.0032 mg/kg/inj; (2) for 0.0032 mg/kg/inj, similar to that of food pellets and significantly higher than cocaine; and (3) decreased after 8 months of daily nicotine self-administration. CONCLUSIONS: These data show that, though high levels of nicotine self-administration can be achieved under simple FR schedules in nonhuman primates, its reinforcing effectiveness is dose-related but limited and may increase over time.
Entities:
Keywords:
Behavioral economics; Exponential model of demand; Fixed ratio; Nicotine self-administration; Nonhuman primates
Authors: E C Donny; A R Caggiula; P P Rowell; M A Gharib; V Maldovan; S Booth; M M Mielke; A Hoffman; S McCallum Journal: Psychopharmacology (Berl) Date: 2000-09 Impact factor: 4.530
Authors: Bernard Le Foll; Svetlana I Chefer; Alane S Kimes; Elliot A Stein; Steven R Goldberg; Alexey G Mukhin Journal: Psychopharmacology (Berl) Date: 2016-02-25 Impact factor: 4.530
Authors: Jack Bergman; Rebecca A Roof; Cheryse A Furman; Jennie L Conroy; Nancy K Mello; David R Sibley; Phil Skolnick Journal: Int J Neuropsychopharmacol Date: 2012-07-25 Impact factor: 5.176
Authors: David S Jacobs; Claire E Barkin; Michelle R Kohut; Jack Bergman; Stephen J Kohut Journal: Drug Alcohol Depend Date: 2017-10-10 Impact factor: 4.492
Authors: Colin S Cunningham; Megan J Moerke; Martin A Javors; F Ivy Carroll; Lance R McMahon Journal: Br J Pharmacol Date: 2016-11-06 Impact factor: 8.739
Authors: John R Smethells; Danielle Burroughs; Amy Saykao; Paul R Pentel; Amir H Rezvani; Mark G LeSage Journal: Drug Alcohol Depend Date: 2020-12-03 Impact factor: 4.492
Authors: Fernando B de Moura; Alexander Sherwood; Thomas E Prisinzano; Carol A Paronis; Jack Bergman; Stephen J Kohut Journal: Pharmacol Biochem Behav Date: 2021-01-12 Impact factor: 3.533