| 1. |
- Löf, Elin, 1974, et al.
(författare)
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Nicotinic acetylcholine receptors are required for the conditioned reinforcing properties of sucrose-associated cues.
- 2010
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Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 1432-2072 .- 0033-3158. ; 212:3, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: We recently demonstrated that blocking specific nicotinic acetylcholine receptors (nAChRs) abolishes the conditioned reinforcing properties of ethanol-associated cues in rat, suggesting nAChRs as promising pharmacological targets for prevention of cue-induced relapse. OBJECTIVES: The present study investigated the involvement of nAChR subtypes in the conditioned reinforcing properties of stimuli associated with a natural reward (sucrose). METHODS: Water-deprived rats were trained to associate a tone + light stimulus (CS) with the presentation of a 0.1 M sucrose solution for 10 consecutive days. On the subsequent day, the animals were tested on the stringent acquisition of a new instrumental response with conditioned reinforcement, following a systemic injection of the nonselective nAChR antagonist mecamylamine (MEC) or the selective alpha7 and alpha6/alpha3beta2beta3* nAChR antagonist methyllycaconitine (MLA). At testing, the rats were presented with two novel levers. Responding on the lever assigned as active (CR lever) resulted in a presentation of the CS alone, while pressing the inactive lever (NCR lever) had no programmed consequences. RESULTS: Control animals pressed the CR lever significantly more than the NCR lever, demonstrating that the CR had acquired conditioned reinforcing properties. Systemic MEC as well as MLA reduced the CR lever responses to the same level as for the NCR lever. CONCLUSIONS: These results demonstrate a role for the alpha7 and/or alpha6/alpha3beta2beta3* nAChRs in conditioned reinforcement to a natural reward and suggest neuronal nAChRs as common mediators of the impact of cues on incentive processes.
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| 2. |
- Löf, Elin, 1974, et al.
(författare)
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Nicotinic acetylcholine receptors in the ventral tegmental area mediate the dopamine activating and reinforcing properties of ethanol cues.
- 2007
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Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 195:3, s. 333-43
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Cues associated with alcohol can elicit craving, support drug-seeking and precipitate relapse. OBJECTIVES: We investigated the possible involvement of nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area (VTA) in the conditioned reinforcing properties of ethanol-associated stimuli in the rat. MATERIALS AND METHODS: First, using in vivo microdialysis, we analyzed the effect of VTA perfusion of the nonselective nAChR antagonist mecamylamine (MEC) or the selective alpha4beta2* nAChR antagonist dihydro-beta-erythroidine (DHbetaE) on the nucleus accumbens (nAc) dopaminergic response to the presentation of an ethanol-associated conditioned stimulus (CS). Second, rats were trained to associate a tone+light CS with the presentation of 10% ethanol and were subsequently tested on the acquisition of a new instrumental response with conditioned reinforcement (CR) after local VTA infusion of MEC, DHbetaE, or alpha-Conotoxin MII (alpha-CtxMII, a selective alpha3beta2* and alpha6* nAChR antagonist). RESULTS: The ethanol-associated CS elevated nAc dopamine, an effect that was blocked by VTA perfusion of MEC but not DHbetaE. Systemic administration of MEC or local VTA infusion of MEC or alpha-CtxMII selectively blocked ethanol-associated CR, whereas systemic DHbetaE had no effect. CONCLUSIONS: We hypothesize a novel mechanism by which alcohol-associated cues promote drug-seeking behavior via activation of dopamine-stimulating alpha-CtxMII-sensitive nAChRs in the VTA. Pharmacological manipulations of selective nAChRs may thus be possible treatment strategies to prevent cue-induced relapse.
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| 3. |
- Narahashi, T, et al.
(författare)
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Mechanisms of alcohol-nicotine interactions: alcoholics versus smokers.
- 2001
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Ingår i: Alcoholism, clinical and experimental research. - 0145-6008. ; 25:5 Suppl ISBRA
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Forskningsöversikt (refereegranskat)abstract
- This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Toshio Narahashi and Bo Söderpalm. The presentations were (1) Nicotinic mechanisms and ethanol reinforcement: Behavioral and neurochemical studies, by Bo Söderpalm, M. Ericson, P. Olausson, and J. A. Engel; (2) Chronic nicotine and ethanol: Differential regulation in gene expression of nicotinic acetylcholine receptor subunits, by X. Zhang and A. Nordberg; (3) Nicotine-ethanol interactions at neuronal nicotinic acetylcholine receptors, by Toshio Narahashi, William Marszalec, and Gary L. Aistrup; (4) Relapse prevention in alcoholics by cigarette smoking? Treatment outcome in an observational study with acamprosate, by L.G. Schmidt, U. Kalouti, M. Smolka, and M. Soyka; and (5) Effect of nicotine on voluntary ethanol intake and development of alcohol dependence in male rats, by L. Hedlund and G. Wahlström.
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| 4. |
- Olausson, Peter, 1971, et al.
(författare)
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Nicotine-induced behavioral disinhibition and ethanol preference correlate after repeated nicotine treatment.
- 2001
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Ingår i: European journal of pharmacology. - 0014-2999. ; 417:1-2, s. 117-23
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the effects of repeated daily nicotine (0.35 mg/kg; 15 days) treatment on behavioral inhibition and locomotor activity in the elevated plus-maze and on voluntary ethanol consumption. When challenged with nicotine before the test, rats pretreated with repeated nicotine spent more time on and made more entries onto the open arms of an elevated plus-maze than did vehicle-pretreated animals. The ethanol preference and intake, measured during 3 h after a nicotine injection, was also higher in the nicotine-pretreated animals. In ethanol consumption experiments, there was a positive correlation between the % time and % entries made onto open arms vs. the ethanol preference and intake. However, no correlation between the total number of entries made in the elevated plus-maze and the measures of ethanol consumption was observed. These findings suggest that the ability of repeated nicotine administration to increase ethanol consumption is related to development of a nicotine-induced reduction of inhibitory control rather than development of locomotor sensitization.
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| 5. |
- Olausson, Peter, 1971
(författare)
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Nicotine sensitization and loss of inhibitory control. Role of serotonin
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Drug dependence is a devastating disorder present in all parts of the world. It is manifested by craving and a general loss of control over the drug intake and the life situation, ultimately leading to compulsive use of the addictive drug at the expense of normal behavioral patterns. This condition is associated with a marked risk for relapse, even after extended periods of drug abstinence. These behavioral impairments have been ascribed the dependence-producing effects of the addictive drugs. The aim of the present thesis was to investigate the effects of subchonic nicotine exposure on animal (rat) behaviors proposed to correlate to craving and drug-taking (i.e. locomotor sensitization) and on brain mechanisms involved in the inhibitory control of such inappropriate motivational impulses and behaviors (i.e. behavioral inhibition). The present experiments demonstrate that repeated treatment with nicotine or amphetamine for 15 consecutive days results in, at least, two distinct behavioral effects: locomotor sensitization and behavioral disinhibition. The expression, but not the induction, of the nicotine-induced behavioral alterations was counteracted by pharmacological manipulations that enhance brain 5-HT neurotransmission. In amphetamine-treated rats, however, these manipulations only antagonized the expression of behavioral disinhibition, and not locomotor sensitization. On the contrary, manipulations that decrease brain 5-HT activity, causing behavioral disinhibition, tended to augment the expression of locomotor sensitization. Behavioral and neurochemical evidence was also obtained indicating that the effects of 5-HT acting drugs on locomotor sensitization and behavioral disinhibition are mediated via distinct neurochemical mechanisms, in which the 5-HT1A and 5-HT2 receptors are differentially involved. Finally, the present experiments demonstrated a strong positive correlation between nicotine-induced behavioral disinhibition and high voluntary ethanol consumption, suggesting that the drug-induced reduction of inhibitory control may have implications for the intake of addictive drugs. Taken together, the findings presented in this thesis indicate that repeated exposure to drugs of abuse concurrently augments the incentive motivational impulse to use the drug and impairs the brain functions involved in inhibitory control of behavior. It is suggested that these drug-induced behavioral changes reflect critical components of the drug-induced neuroadaptive processes which ultimately lead to compulsive drug use, and the pharmacological treatments which antagonized the expression of these behavioral impairments may have beneficial effects in the treatment of drug abuse.
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