Modification of place preference conditioning in mice by systemically administered [Leu]enkephalin

doi:10.1016/0166-4328(86)90069-0

Behavioural Brain Research

Volume 22, Issue 3, December 1986, Pages 249-255

https://doi.org/10.1016/0166-4328(86)90069-0 Get rights and content

Abstract

[Leu]enkephalin (300 μg/kg, i.p.) induced either a positive or negative conditioned place preference response in mice depending on whether the animals were trained against or towards their initial preference. Induction of a positive preference (300 μg/kg) was partially blocked by simultaneous addition of methylnaloxonium (10 mg/kg, i.p.), an opoid antagonist that does not readily cross the blood-brain barrier; methylnaloxonium alone (3 or 10 mg/kg) had no effect on the place preference response. The results indicate that [Leu]enkephalin treatment reverses the initial preference of the animal regardless of training, and that some aspect of the [Leu]enkephalin effect on place preference conditioning is mediated by peripheral opioid receptors. These findings challenge the notion that place preference conditioning is a simple measure of opioid reward.

References (30)

M.T. Bardo et al.
Conditioned place preference with morphine: the effect of extinction training on the reinforcing CR
Pharmacol., Biochem. Behav.
(1984)
J.D. Belluzzi et al.
Facilitation of long-term memory by brain endorphins
A. Bianchetti et al.
Quarternary derivatives of narcotic antagonists: stereochemical requirements at the chiral nitrogen for in vitro and in vivo activity
Life Sci.
(1983)
M. Gallagher et al.
Enkephalin analogue effects in the amygdala central nucleus on conditioned heart rate
Pharmacol. Biochem. Behav.
(1982)
D. Gilbert et al.
B-phenylethylamine-, d-amphetamine- and l-amphetamine-induced place preference conditioning in rats
Eur. J. of Pharmacol.
(1983)
J. Hughes
Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine
Brain Res.
(1975)
I. Izquierdo et al.
Post-training intraperitoneal administration of Leu-enkephalin and β-endorphin causes retrograde amnesia for two different tasks in rats
Behav. Neural Biochem.
(1980)
A.J. Kastin et al.
Enkephalin and a potent analog facilitate maze performance after intraperitoneal administration in rats
Pharmacol. Biochem. Behav.
(1976)
J.L. Martinez et al.
Enkephalin actions on avoidance conditioning may be related to adrenal medullary function
Behav. Brain Res.
(1982)
J.L. Martinez et al.
Central versus peripheral actions of Leu-enkephalin on acquisition of a one-way active avoidance response in rats
Brain Res.
(1985)

J.L. Martinez et al.

Endorphin and enkephalin effects on avoidance conditioning: the other side of the pituitary-adrenal axis

J.L. Martinez et al.

Leu-enkephalin actions on avoidance conditioning are mediated by a peripheral opioid mechanism

Life Sci.

(1985)

G.A. Olson et al.

Effects of an enkephalin analog on complex learning in the rhesus monkey

Pharmacol. Biochem. Behav.

(1979)

S. Schenk et al.

An examination of heroin conditioning in preferred and non-preferred environments and in differentially housed mature and immature rats

Pharmacol. Biochem. Behav.

(1985)

N.R. Swerdlow et al.

Electrolytic lesions of the substantia innominata and lateral preoptic area attenuate the ‘supersensitive’ locomotor response to apomorphine resulting from denervation of the nucleus accumbens

Brain Res.

(1984)

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Conditioned place preferences induced by hearing song outside the breeding season relate to neural dopamine D<inf>1</inf> and cannabinoid CB<inf>1</inf> receptor gene expression in female European starlings (Sturnus vulgaris)
2019, Behavioural Brain Research
Citation Excerpt :
In the case of starlings specifically, past studies show that female starlings in overwintering flocks share song types with close neighbors [49], which suggests that neighbor song may be more biologically relevant than the unfamiliar song stimuli that we used in this study. Past CPP studies show that whether an animal is conditioned towards or against its initial stimulus/compartment preference (as determined during baseline testing) can influence the development of place preferences [50–53]. Consistent with this possibility, female starlings demonstrated a significant song-induced place aversion only when song was paired with the CPP compartment that was initially preferred (as measured during habituation).
The affective state induced by sensory stimuli changes to adaptively modify behaviors that are critical for survival and reproduction. In European starlings, during the spring breeding season, male courtship song is rewarding to females, but only to those that possess resources that are necessary for reproduction (i.e., nesting sites). In fall, starling song is non-sexual and proposed to maintain flocks. This suggests that in fall it may be adaptive for females to be rewarded by fall rather than spring, courtship song. We used a conditioned place preference (CPP) test to evaluate song-induced affective state in fall condition females and quantitative real-time PCR to measure expression of genes that modulate affective state (CB₁ endocannabinoid and D₁ dopamine receptors) in brain regions that were previously implicated in song-induced reward (i.e., the medial preoptic nucleus (mPOA) and ventromedial hypothalamus (VMH)). Fall condition females developed an aversion to a place that had been paired with playback of both male fall and courtship song, indicating that in general male song induces a negative affective state outside the breeding season. Song-induced aversion was stronger in birds conditioned towards an initial place preference. For mPOA, CB₁ receptor expression correlated positively with fall and spring song-induced CPP. D₁ receptor expression correlated negatively with fall (but not spring) song-induced CPP, and the ratio of CB₁ to D₁ receptor expression correlated positively with fall (but not spring) song-induced CPP. These correlations suggest that interactions between D₁ and CB₁ receptors in mPOA may play a role in modifying affective responses to song.
Prenatal exposure to cocaine alters the development of conditioned place-preference to cocaine in adult mice
2007, Pharmacology Biochemistry and Behavior
As addiction is increasingly formulated as a developmental disorder, identifying how early developmental exposures influence later responses to drugs of abuse is important to our understanding of substance abuse neurobiology. We have previously identified behavioral changes in adult mice following gestational exposure to cocaine that differ when assessed with methods employing contingent and non-contingent drug administration. We sought to clarify this distinction using a Pavlovian behavioral measure, conditioned place-preference. Adult mice exposed to cocaine in utero (40 or 20 mg/kg/day), vehicle and pair-fed controls were place-conditioned to either cocaine (5 mg/kg or 20 mg/kg, i.p.) or saline injections. The development of conditioned place-preference to cocaine was impaired in mice exposed to cocaine in utero, and was abolished by fetal malnutrition. A context-specific place-aversion to vehicle but not cocaine injection was observed in prenatally cocaine-exposed mice. Locomotor behavior did not differ among prenatal treatment groups. We conclude that early developmental exposure to cocaine may diminish the subsequent rewarding effects of cocaine in adulthood measured with classical conditioning techniques, and that this is not due to changes in locomotor behavior. Sensitivity to acute stress is also altered by prenatal cocaine exposure, consistent with earlier findings in this model.
Conditioned place preference induced by morphine and morphine-6-glucuronide in mice
2006, Pharmacology Biochemistry and Behavior
Morphine-6-glucuronide (M6G), an active metabolite of morphine has been shown to produce analgesia and fewer side effects than morphine, and the introduction of M6G as a new drug for treatment of postoperative pain is planned in 2007. Following morphine intake in humans, the metabolites morphine-3-glucuronide (M3G) and M6G are present in substantial concentrations and for longer periods than the parent drug. The possible reward effects of the morphine glucuronides have previously not been well studied. In the present study, conditioned place preference (CPP) was recorded after conditioning with subcutaneous injections of 5, 10, 20, 30 or 50 μmol/kg morphine or M6G, or 240 or 500 μmol/kg M3G in C57BL/6J-Bom mice, using a biased two compartment (“closed” and “open”) counterbalanced paradigm.
CPP was induced after treatment with both morphine and M6G with dose dependent increase up to 30 μmol/kg after treatment in the “closed” compartment. No dose response was observed in the “open” compartment, with maximal CPP after 10 μmol/kg morphine or M6G.
M3G caused a tendency of condition place aversion (CPA), although not statistically significant. In the present study morphine and M6G demonstrated comparable reward effects, at doses that differed depending on which compartment the mice were conditioned in. M3G showed a tendency to exhibit aversive properties.
Apparatus bias and the use of light and texture in place conditioning
2005, Pharmacology Biochemistry and Behavior
In a typical conditioned place preference (CPP) preparation, animals alternately experience drug and vehicle effects in distinct chambers of an apparatus, spending more time in the drug-paired chamber post-conditioning. However, if all animals prefer the same chamber before conditioning, data interpretation may be compromised. Unbiased apparatus has been systematically validated with ethanol in mice ([Cunningham, C.L., Feree, N.K., Howard, M.A. Apparatus bias and place conditioning with ethanol in mice. Psychopharmacology (Berl) 2003;170:409–422]); the present study sought to identify and eliminate bias in a standard black-and-white apparatus and validate that apparatus for CPP with morphine and cocaine in rats. Apparatus bias was assessed in 24 adult female Sprague–Dawley rats. Subjects preferred the black chamber under bright lighting conditions, with no preference in the dark. Subjects then underwent a counterbalanced CPP regimen to 5 mg/kg SC morphine (n = 12) or 20 mg/kg IP cocaine (n = 12) using only tactile conditioned stimuli. Significant absolute preferences for the drug-paired chamber were produced by both drugs, with no effect of drug-paired chamber assignment on CPP expression; vehicle-treated controls (n = 12) showed no preferences. Bias-free CPP to morphine and cocaine using standard apparatus in rats is possible. Implications for place conditioning are discussed, including the potential value of systematically exploiting apparatus bias in addition to eliminating it.
Evidence for changes in brain enkephalin contents associated to male rat sexual activity
2002, Behavioural Brain Research
Indirect evidence suggests that ejaculation might activate endogenous opioid systems, which exert an inhibitory influence on male rat sexual behaviour. The objective of the present study was to search for putative long-term changes in the contents of immunoreactive (IR) Met-enkephalin (IR-Met), Leu-enkephalin (IR-Leu) and opioid octapeptide Met–Arg⁶–Gly⁷–Leu⁸ (IR-Oct) in specific brain areas, after the execution of different amounts of sexual activity. Additionally, basal contents of these enkephalins were compared between sexually active (SA) and persistent sexually inactive (SI) rats. Immunoreactivity to enkephalins was determined by radioimmunoanalysis, in the frontal cortex, the hypothalamus and midbrain of SA and SI rats, as well as 24 or 48 h after males had one ejaculation or copulated to exhaustion. Twenty-four hours after sexual activity, there was a generalised increase in enkephalin contents that returned to control values at the 48 h measurement in all brain areas, but the hypothalamus, where IR-Met and IR-Oct remained elevated. No differences in the magnitude of the changes were found between rats that ejaculated once and sexually satiated males. IR-Oct concentration in the hypothalamus of SI rats appeared significantly higher than in SA animals, with no differences in IR-Met and IR-Leu. Results give direct evidence of the activation of endogenous opioid systems by male rat sexual activity. The occurrence of long lasting increases in the contents of IR-Met and IR-Oct in the hypothalamus of rats that copulated was detected. Finally, an intrinsically elevated octapeptide concentration in the hypothalamus of SI rats was found.
Cocaine and morphine-induced place conditioning in adolescent and adult rats
2000, Physiology and Behavior
The periadolescent period in the rat is characterized by alterations in novelty seeking and exploratory behavior, as well as changes in the behavioral responsiveness to many drugs of abuse. These alterations may be predictive of alterations in the reward value of drugs of abuse. The present experiments examined whether adolescent rats (34–37 days old) differ from their adult counterparts in the expression of drug-induced place conditioning for morphine (0, 2.5, or 5 mg/kg; Experiment I) and cocaine (0, 5, or 10 mg/kg; Experiments II and III). Animals received multiple conditioning days, followed 24 h later by a drug-free CPP test. All drugs were given intraperitoneally immediately prior to confinement in the CS+ compartment, while vehicle injections were given prior to exposure to the CS− chamber. For both drugs, there were no significant differences between adolescents and adults in amount of place conditioning seen when drug exposure was paired with the nonpreferred chamber. When cocaine was paired with either the preferred or nonpreferred compartment (Experiment III), again, the magnitude of the place conditioning observed did not differ between adolescents and adults. The lack of age differences in expression of drug-induced place conditioning in the present experiments is not likely a result of ceiling effects, because the data suggest that the doses used included near-threshold doses. Although these findings need to be confirmed using other approaches for assessing drug reward before concluding that adolescent and adult rats exhibit similar sensitivity to the rewarding effects of morphine and cocaine, the current data revealed no differences between adolescents and adults in the magnitude of place conditioning expressed for morphine or cocaine.

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Research paperModification of place preference conditioning in mice by systemically administered [Leu]enkephalin

Abstract

Pharmacol., Biochem. Behav.

Life Sci.

Pharmacol. Biochem. Behav.

Eur. J. of Pharmacol.

Brain Res.

Behav. Neural Biochem.

Pharmacol. Biochem. Behav.

Behav. Brain Res.

Brain Res.

Life Sci.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Brain Res.

Research paper
Modification of place preference conditioning in mice by systemically administered [Leu]enkephalin