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Aims Continuous morphine consumption contributes to the development of cognitive disorders. This work investigates the impacts of different types of exercise on learning and memory in morphine-dependent rats. Main methods Forty morphine-dependent rats were randomly divided into five groups: sedentary-dependent (Sed-D), endurance exercise-dependent (En-D), strength exercise-dependent (St-D), and combined (concurrent) exercise-dependent (Co-D). Healthy rats were used as controls (Con). After 10 weeks of regular exercise (endurance, strength, and concurrent; each five days per week), spatial and aversive learning and memory were assessed using the Morris water maze and shuttle box tests. Key findings The results showed that morphine addiction contributes to deficits in spatial learning and memory. Furthermore, each form of exercise training restored spatial learning and memory performance in morphine-dependent rats to levels similar to those of healthy controls. Aversive learning and memory during the acquisition phase were not affected by morphine addiction or exercise, but were significantly decreased by morphine dependence. Only concurrent training returned the time spent in the dark compartment in the shuttle box test to control levels. Significance These findings show that different types of exercise exert similar effects on spatial learning and memory, but show distinct effects on aversive learning and memory. Further, morphine dependence-induced deficits in cognitive function were blocked by exercise. Therefore, different exercise regimens may represent practical treatment methods for cognitive and behavioral impairments associated with morphine-related disease.

This study demonstrates that, during morphine addiction and withdrawal in rats profound alterations in the concentrations of a variety of brain peptides occur. Somatostatin, cholecystokinin, neurotensin and substance P concentrations increased during morphine addiction. Naloxone-induced withdrawal decreased brain concentrations of TRH, somatostatin, neurotensin and substance P. Naloxone alone decreased thalamic substance P and neurotensin concentrations. Vasoactive intestinal peptide concentrations were unaltered by any of the treatments. The fall in the tissue concentration of somatostatin during naloxone-induced withdrawal correlated well with the fall in the circulating growth hormone, suggesting that this could be secondary to somatostatin release. Our data support the hypothesis that brain peptides, acting locally in the brain as neuromodulators, play an important role in the genesis of the syndromes of morphine addiction and withdrawal.

Developmental, neuroendocrine and behavioral effects of early morphine addiction in female rat pups were investigated. compared with controls, body weights of morphine-injected animals, regardless of treatment age, were depressed during treatment and remained depressed for periods up to 49 days; growth rates of these animals were decreased during drug treatment but temporarily surpassed those of controls following termination of morphine administration. Delayed eye opening and early vaginal opening occurred in some of the animals administered morphine before Day 14. Behaviorally, animals treated with the narcotic from Days 15–21 showed impaired activity in the open field test; all animals, in any early morphine treatment group, showed normal resting pituitary-adrenal activity at 30 days of age and showed no neuroendocrine signs of protracted dependence. However, rats neonatally narcotic-treated on Days 15–21 showed a decreased corticosterone rise in response to morphine challenge of 30 mg/kg for as late as Day 62. The persistence of the weight and endocrine effects suggest that exposure of the immature female rat to morphine results in prolonged morphine-specific alteration of brain mechanisms concerned with behavioral and neuroendocrine processes and supports the suitability of using a rat model to study long-term effects of neonatal narcotic addiction.

Several biogenic amines have been suggested to play a possible role in opiate addiction. While some reports indicated changes in brain norepinephrine and dopamine concentrations and/or synthesis (1,2,3), others have demonstrated the involvement of serotonin or acetylcholine (4,5,6,7). In view of recent reports suggesting a possible role for histamine in brain function as another putative neurotransmitter (8), we have investigated whether this biogenic amine might also participate in morphine addiction and withdrawal.