Abstract
Individual differences in behavioral characteristics or initial responses to abused drugs had been recently demonstrated to have predictive value in the propensity of later abuse. The research described here was initiated to determine the initial response of rats to administration of morphine if the physiological response has predictive value for the propensity of the animals to later self-administration. The initial response of extracellular fluid levels of the biogenic monoamine neurotransmitters in the anterior cingulate cortex (aCC) was assessed in drug rats with in vivo microdialysis following administration of morphine. Rats that did not acquire morphine self-administration (NSA) had higher baseline levels of aCC extracellular fluid levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) than animals that developed stable morphine self-administration (SA). However, the response independent administration of morphine resulted in a dramatic increase in (DA) in aCC in the SA group, while the morphine injection in the NSA rats increased extracellular fluid levels of noradrenaline (NA). It is possible that these differences might be related to the development of physical dependence. Therefore, the development of physical dependence was observed in these animals. There was no relationship between the propensity to self-administration morphine and the development of physical dependence. Rats that showed the highest withdrawal scores had lower extracellular fluid levels of serotonin (5-HT) compared to rats showing low withdrawal scores. Thus, monoamine neuronal innervations of the aCC respond to an initial dose of morphine that is predictive of the later propensity to self-administration and the resistance and predisposition to the formation of opiate dependence, but there is no relationship between these two indices in individual animals. These data add to a growing body of evidence for the involvement of neuronal systems in the aCC in the actions of opiates.
Highlights
There is a significant degree of variability in the vulnerability of individuals to escalate drug intake from recreational use to abuse and data from the animal laboratory has identified mechanisms that may be responsible for some of these differences
Acquisition of Morphine Self-administration Response independent administration of morphine did not alter the concentration of the monoamine neurotransmitters or metabolites compared to baseline levels (Figure 1), when the data were segregated based upon the propensity of each rat to acquire morphine self-administration, significant differences became apparent
There were no significant differences in DA and dihydroxyphenylacetic acid (DOPAC) between the two baseline samples for individual animals, the content of the test substances in the second baseline sample was used for each animal as baseline which was compared with the values obtained after the administration of morphine
Summary
There is a significant degree of variability in the vulnerability of individuals to escalate drug intake from recreational use to abuse and data from the animal laboratory has identified mechanisms that may be responsible for some of these differences. A relationship between emotionality and the acquisition of drug self-administration was demonstrated in the animal laboratory. It has been shown that stress induced locomotor activity [1] or corticosterone levels [2] was predictive of individual variability to a later response to amphetamine in rats. The locomotor response to a novel environment appears to have predictive value in morphine intake in rats during the first five days of acquisition of self-administration [3]. Emotionality in the lick suppression test is correlated with later morphine self-administration in rats [5]
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