Matthew Palmatier | East Tennessee State University (original) (raw)

Papers by Matthew Palmatier

Nebraska Symposium on Motivation. Nebraska Symposium on Motivation, 2009

Models of intravenous nicotine self-administration in laboratory animals are being used to invest... more Models of intravenous nicotine self-administration in laboratory animals are being used to investigate the behavioral and neurobiological consequences of nicotine reinforcement, and to aid in the development of novel pharmacotherapies for smoking cessation. Central to these models is the principle of primary reinforcement, which posits that response-contingent presentation of a primary reinforcer, nicotine, engenders robust operant behavior, whereas response-independent drug delivery does not. This dictum of nicotine as a primary reinforcer has been widely used to explain why people smoke tobacco-smoking results in the rapid delivery of nicotine to the brain, setting up a cascade of neurobiological processes that strengthen subsequent smoking behavior. However, there is mounting evidence that the primary reinforcement model of nicotine self-administration fails to fully explain existing data from both the animal self-administration and human smoking literatures. We have recently pro...

Behavioural brain research, Jan 25, 2007

Three experiments examined the effects of drug-extinction when a drug state served as a condition... more Three experiments examined the effects of drug-extinction when a drug state served as a conditional stimulus (CS) for sucrose delivery or as a positive feature for pairings between a discrete CS (e.g., 15-s light-on) and sucrose. Some conditioning models predict that drug state will facilitate the conditional response (CR) based on an association with sucrose whether the drug is trained as a CS or as a facilitator. If so, repeated presentation of the drug state alone (drug-extinction) should decrease the CR in both situations. Nicotine (0.4mg/kg), amphetamine (AMP, 1mg/kg), and chlordiazepoxide (CDP, 5mg/kg) facilitated a goal tracking conditioned response to the discrete CS; however, AMP and CDP did not evoke reliable responding without an interposed stimulus, suggesting that associations between these drug states and sucrose are not expressed as anticipatory food seeking (goal tracking). Repeated presentation of each drug state alone did not disrupt facilitation by nicotine, amphe...

Neuropsychobiology, 2002

In rats, a distinct environment repeatedly paired with nicotine (0.421 mg/kg base, s.c.) comes to... more In rats, a distinct environment repeatedly paired with nicotine (0.421 mg/kg base, s.c.) comes to evoke an increase in activity in the absence of any drug. This hyperactivity indicates a Pavlovian-conditioned association between the environment and nicotine. We investigated whether a dopamine D(1) receptor antagonist (SCH-23390), a D(2)/D(3) antagonist (eticlopride) or a GABA(B) agonist (baclofen) would prevent the acquisition of nicotine-conditioned hyperactivity. In saline-pretreated rats, acute nicotine suppressed activity during the conditioning phase (i.e. environment-nicotine pairings); chronic nicotine stimulated activity. Pretreatment with SCH-23390 (0.01 mg/kg, i.p.) attenuated the activating effects of nicotine without affecting controls. Eticlopride (0.03-0.07 mg/kg, i.p.) and baclofen (0.625 and 1.25 mg/kg, i.p.) did not affect nicotine-induced activity in a selective manner. Regardless of the pretreatment drug, rats acquired the environment-nicotine association as index...

Animal Learning & Behavior, 1999

The effect of an auditory cue presented during extinction on spontaneous recovery of a conditione... more The effect of an auditory cue presented during extinction on spontaneous recovery of a conditioned taste aversion was investigated in three experiments. Experiment 1 demonstrated that the presence of the cue during extinction did not influence saccharin consumption during that phase, and that an aversion to saccharin in the absence of the cue was stronger at 18 days than at 1 day after extinction, representing spontaneous recovery rather than a renewal effect. Experiment 2 showed that a cue presented during extinction and testing reduced spontaneous recovery. Experiment 3 replicated that effect and showed that it depended on the cue's correlation with extinction and not on an unconditioned effect; cues that had been presented during or prior to conditioning did not reduce spontaneous recovery when presented during testing. The cue's potential to reduce spontaneous recovery through conditioned inhibition or configural cue learning is discussed, as is the possibility that the cue retrieves a saccharin extinction memory in a manner consistent with Bouton's (1993) account of spontaneous recovery.

Psychopharmacology, 2014

Rationale Varenicline (VAR), a smoking cessation aid that is a partial agonist at nicotinic recep... more Rationale Varenicline (VAR), a smoking cessation aid that is a partial agonist at nicotinic receptors, mimics the reinforcement-enhancing effects of nicotine. Varenicline, when accompanied by non-drug cues, is self-administered by rats, though it is unclear whether this results from varenicline acting as a primary reinforcer or a reinforcement enhancer of the cues. Objectives This study sought to disentangle these two potential actions. Methods Rats were allowed to self-administer intravenous nicotine, saline, or varenicline during 1-h sessions in operant chambers equipped with two levers. Five groups had concurrent access to drug infusions and a moderately reinforcing visual stimulus (VS) for responding on separate levers. Meeting the reinforcement schedule on one lever was reinforced with VAR (0.01, 0.06, 0.1 mg/kg/infusion), nicotine (0.06 mg/kg/infusion), or saline, while meeting the same schedule on the other lever delivered the VS. Additional groups were reinforced for pressing a single "active" lever and received VAR paired with the VS, the VS with response-independent infusions of VAR, or VAR alone (0.1 mg/kg/ infusion). Results Rats readily responded for VAR paired with VS on a single lever. However, when VAR was the only reinforcer contingent on a response, rats did not respond more than for saline. Conclusions These findings show that VAR does not serve as a primary reinforcer in rats at doses that increase responding for non-drug reinforcers. These data are consistent with research showing that the primary reinforcing effects of VAR are weak, at best, and that the primary reinforcing and reinforcement-enhancing actions of nicotinic drugs are pharmacologically distinct.

Behavioural brain research, Jan 15, 2014

This study analyzed sex differences in methylphenidate (MPH) sensitization and corresponding chan... more This study analyzed sex differences in methylphenidate (MPH) sensitization and corresponding changes in glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotprhic factor protein (BDNF) in adolescent male and female rats. After habituation to a locomotor arena, animals were sensitized to MPH (5mg/kg) or saline from postnatal day (P) 33-49, tested every second day. On P50, one group of animals were injected with saline and behavior assessed for conditioned hyperactivity. Brain tissue was harvested on P51 and analyzed for GDNF protein. A second group of animals was also sensitized to MPH from P33 to 49, and expression of behavioral sensitization was analyzed on a challenge given at P60, and BDNF protein analyzed at P61. Females demonstrated more robust sensitization to MPH than males, but only females given MPH during sensitization demonstrated conditioned hyperactivity. Interestingly, MPH resulted in a significant increase in striatal and accumbal GDNF with no sex dif...

Pharmacology, biochemistry, and behavior, 2014

Nicotine is a psychomotor stimulant with 'reinforcement enhancing' effects--the actions o... more Nicotine is a psychomotor stimulant with 'reinforcement enhancing' effects--the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30s illumination of a light or presentation of a lever) was immediately followed by a sweet reward deliver...

Encyclopedia of Psychopharmacology, 2010

Psychopharmacology, 2006

Rationale: Nicotine has two effects on reinforcement in traditional self-administration paradigms... more Rationale: Nicotine has two effects on reinforcement in traditional self-administration paradigms. It serves as a primary reinforcer by increasing the probability of behaviors that result in nicotine delivery. However, nicotine also potently enhances behaviors that result in the delivery of nonpharmacological reinforcers. Objectives: The present study sought to dissociate these two effects of nicotine on reinforcement. Methods: For one group of rats (2 lever), a nonpharmacological reinforcer [visual stimulus (VS)] was available for pressing one lever. Nicotine infusions were available for pressing a different lever. A second group (NIC + VS) received more traditional selfadministration training; both the VS and nicotine were delivered for pressing a single active lever. Control groups received either nicotine infusions (NIC only) or VS presentations (VS only) for pressing the active lever. Results: Nicotine alone was a weak reinforcer; the VS alone was slightly more reinforcing than nicotine. When these two reinforcers were combined (NIC + VS), response rates were synergistically increased. For the 2-lever group, responding on the nicotine lever was weak, matching the response rates of rats receiving nicotine alone. However, responding on the VS lever was potently enhanced in this group; equaling the response rates for rats receiving both reinforcers for making a single response (NIC + VS). Conclusions: These data indicate that the reinforcementenhancing effects of nicotine are very potent even when only moderate quantities of the drug are self-administered. Moreover, they provide the first demonstration that the reinforcement-enhancing and primary reinforcing effects of nicotine can be dissociated behaviorally.

Psychopharmacology, 2013

Nicotine (NIC) potently increases operant responding for non-NIC reinforcers, and this effect may... more Nicotine (NIC) potently increases operant responding for non-NIC reinforcers, and this effect may depend on drug-mediated increases in incentive motivation. According to this hypothesis, NIC should also potently increase approach to Pavlovian-conditioned stimuli associated with rewards. The present studies explored the effects of NIC on Pavlovian-conditioned approach responses. To do so, liquid dippers were used to deliver an unconditioned stimulus (US; 0.1 ml sucrose) after presentation of a conditioned stimulus (CS; 30 s illumination of a stimulus light)-both the CS and US were presented in receptacles equipped to monitor head entries. In experiment 1, the CS and US were presented in the same receptacle, but NIC pretreatment (0.4 mg/kg base) did not increase conditioned approach responses. Delivery of the sucrose US was then shifted to receptacle in a different location. All rats learned to approach the new US location (goal-tracking) at similar rates. Approach to the CS receptacle (sign-tracking) declined for saline-pretreated rats, but NIC pretreatment increased sign-tracking. In experiment 2, NIC pretreatment increased sign-tracking when the CS and US were spatially separated during acquisition. In experiment 3, NIC pretreatments were replaced with saline, but the effect of NIC persisted for an additional 24 test sessions. The findings suggest that NIC increases incentive motivation and that this effect is long-lasting, persisting beyond the pharmacological effects of NIC.

Psychopharmacology, 2008

The motivational effects of nicotine-associated cues have been demonstrated in animal studies. Ho... more The motivational effects of nicotine-associated cues have been demonstrated in animal studies. However, it is unknown whether the effectiveness of nicotine cues in reinstating nicotineseeking varies with the extent of prior nicotine self-administration. In addition, the issue of whether bupropion (an FDA-approved smoking cessation medication) interferes with the conditioned incentive of nicotine cues remains to be addressed.