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J L Neisewander

Publications and source records attributed to J L Neisewander.

43 records · Page 3Linked to original sources

Repeated testing attenuates conditioned place preference with cocaine.

Cocaine-treated rats acquired a preference for cocaine-associated contextual stimuli (CS) relative to saline-injected control rats. However, when animals were given repeated tests for conditioned place preference intermittent between conditioning trials, they displayed an attenuation in strength of conditioning. This attenuation was not due to pharmacologic tolerance (Experiment 1), but rather reflected a disruption in learning due to exposure to the CS alone (Experiment 2). Like other examples of classical conditioning, the strength of the conditioned response (CR) as assessed by the conditioned place preference model may be influenced by partial reinforcement.

Animals↗

Single-trial conditioned place preference using intravenous morphine.

Experiments were performed to investigate single-trial conditioned place preference (CPP) using intravenous morphine in rats. Single-trial CPP was obtained when morphine (8 mg/kg) was paired for either 15 or 30 min with a distinct white compartment. When morphine administration was delayed for either 15 or 25 min after the beginning of a 30-min exposure to the white compartment, single-trial CPP was not obtained. Intravenous naloxone (2 mg/kg) also blocked single-trial CPP when administered 15 min after the beginning of the 30-min exposure to the white compartment with morphine, but naloxone by itself did not alter place preference. The results from these experiments indicate that single-trial CPP using intravenous morphine may offer a useful animal model to assess the reinforcing efficacy of the initial drug experience.

Animals↗

Disruption of neophobia, conditioned odor aversion, and conditioned taste aversion in rats with hippocampal lesions.

Previous studies have implicated the hippocampus in the acquisition of conditioned taste aversions. However, the effect of hippocampal (HPC) lesions on the acquisition of conditioned aversions to the distal olfactory cue has not been investigated. In this study rats with bilateral electrolytic hippocampal lesions were given access to an odor conditioned stimulus (CS) alone or a compound odor-taste CS, followed by an injection of LiCl or saline. The results indicated that HPC lesions attenuated the neophobic response to both CSs, and disrupted conditioned odor and taste aversions, relative to sham-operated controls. Furthermore, the disruption in conditioned odor aversions could not be attributed to attenuation of neophobia in lesioned subjects nor to prolonged neophobia in sham-operated controls. The results are consistent with pharmacological studies in suggesting that the hippocampus is involved in the formation of conditioned odor aversions.

Animals↗

Conditioned place preference with morphine: the effect of extinction training on the reinforcing CR.

Rats were injected with either morphine (5 mg/kg) or saline in association with one set of distinct environmental stimuli, and injected with saline in association with a different set of stimuli. After four conditioning trials, animals were given a 15-minute free-choice test to determine which stimulus environment was preferred. Animals displayed CPP as a significant increase in duration spent within the morphine-associated environment, but did not display any change in number of entries into that environment. In contrast, when extinction training was given following CPP, animals displayed a significant decrease in duration spent per entry into the morphine-associated environment, but did not display any change in total duration spent in that environment. These results suggest that assessment of the reinforcing conditioned response (CR) in the CPP model may require measurement of both duration spent in and number of entries into the drug-associated environment.

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Impaired supersensitivity to morphine following chronic naltrexone treatment in senescent rats.

Chronic administration of opiate antagonists produces an increase in the density of opiate receptors, as well as an enhanced sensitivity to the analgesic and locomotor depressant effects of morphine. The present study assessed whether aging alters these regulatory processes. Young (3-4 months), middle-aged (10-11 months), and senescent (25-30 months) rats were implanted subdermally with slow-release naltrexone pellets or were given sham surgery. The pellets were removed 10 days later. Twenty-four hours after pellet removal, morphine-induced (5 mg/kg, SC) analgesia and locomotor activity were assessed. Young and middle-aged rats treated with naltrexone showed enhanced sensitivity to the analgesic and locomotor activity depressant effects of morphine relative to age-matched controls. In contrast, senescent rats treated with naltrexone did not differ from age-matched controls in their response to morphine. The density of opiate receptors labeled with 3H-naloxone was measured in the anterior striatum. Both young and senescent rats treated with naltrexone exhibited an increase in opiate receptor density relative to age-matched controls. The results indicate that senescent rats are capable of up-regulating opiate receptors following chronic naltrexone treatment but do not exhibit the corresponding functional supersensitivity to morphine.

Aging↗

Passive exposure to a contextual discriminative stimulus reinstates cocaine-seeking behavior in rats.

A significant problem in treating cocaine dependence is craving-induced relapse elicited by inadvertent (i.e., passive) exposure to cocaine-paired stimuli. Extinction/reinstatement of cocaine-seeking behavior in animals has been used to investigate this phenomenon. Most studies using this model have examined reinstatement by response-contingent exposure to discrete cocaine-paired stimuli. The present study expanded this research by examining passive (i.e., not contingent upon an operant response) exposure to a contextual cocaine-paired stimulus to better model craving elicited by inadvertent exposure to cocaine-associated environmental stimuli. Rats underwent daily cocaine and saline self-administration sessions that were identical to each other except for a discriminative stimulus (scented bedding) signaling cocaine availability (S+) or nonavailability (S-). Subsequently, they were placed into the self-administration chambers in the presence of neutral bedding. Reinforcement was not available and cocaine-seeking behavior (i.e., nonreinforced operant responses) was extinguished across days. Rats were then reintroduced to the S+ and S- stimuli. Presentation of the S+, but not the S-, elicited significant reinstatement of cocaine-seeking behavior. The results demonstrate that passive exposure to a contextual discriminative stimulus reinstates extinguished cocaine-seeking behavior. Furthermore, we suggest that reinstatement of cocaine-seeking behavior by passive exposure to cocaine-paired stimuli may provide a model of craving-induced relapse elicited by inadvertent exposure to a cocaine-associated environment.

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Up-regulation of opiate receptors following chronic naloxone treatment in aged rats.

The present study assessed whether there are age-dependent differences in up-regulation of opiate receptors following chronic naloxone treatment in mature (3 months) and aged (27 months) male Wistar rats. Half of each age group were implanted subdermally with slow-release naloxone pellets for 10 days, and half were given sham surgery. Twenty-four hours after pellet removal, the rats were decapitated and various CNS areas including spinal cord, hindbrain, midbrain, diencephalon, hippocampus, striatum, olfactory tubercles/nucleus accumbens and prefrontal cortex were dissected and assayed for [3H]naloxone binding. The results indicated that aged rats had fewer opiate receptors in the spinal cord, midbrain, striatum, and olfactory tubercle/nucleus accumbens. Despite this age-related decline in opiate receptors, aged rats showed an up-regulation response similar to mature rats in all areas except the hippocampus of the left hemisphere, where they showed enhanced up-regulation relative to mature rats. The maintained plasticity of the opioid system contrasts with findings in other receptors systems where age-related impairments of antagonist-induced up-regulation have been reported.

Aging↗