TY - JOUR
T1 - A single-day paradigm of self-regulated human cocaine administration
AU - Matuskey, D.
AU - Pittman, B.
AU - Chen, J. I.
AU - Wanyiri, J.
AU - Nadim, H.
AU - Jatlow, P.
AU - Gueorguieva, R.
AU - Potenza, M. N.
AU - Morgan, P. T.
AU - Bhagwagar, Z.
AU - Malison, R. T.
N1 - Funding Information:
We would like to thank the staff of the Clinical Neuroscience Research Unit (CNRU) at CMHC and the Hospital Research Unit (HRU) in YNHH. This work was supported by the National Institute on Drug Abuse (NIDA; K24 DA017899 ; R03 DA025176 ; RTM; P20 DA027844 ; MNP), the National Institute of Mental Health (NIMH; T32 MH019961 ; DM/RTM), Yale Center for Clinical Investigation (YCCI) Pilot Projects Translational and Interdisciplinary Research and the Department of Mental Health and Addiction Services of the State of Connecticut .
PY - 2012/11
Y1 - 2012/11
N2 - Prior work by our group has shown the feasibility, safety, and validity of a multi-day, multi-dose paradigm of self-regulated cocaine administration in humans. The current work sought to consolidate these methods in a single-day design focused on reducing logistical complexity, decreasing research burden to human subjects, and increasing suitability for medication development designs. Methods: Eleven experienced cocaine users participated in a 6-hour, single-day design, consisting of one safety/eligibility and three experimental cocaine periods (during which subjects were allowed to self-administer 8, 16, and 32 mg/70 kg cocaine doses under a fixed-ratio 1:5 minute timeout schedule). Changes in cocaine-induced cardiovascular response, self-administration behavior, and subjective effects were assessed. Results: Procedures were well tolerated by participants, and no significant adverse events were noted. Significant (p < 0.05), changes in measures of cocaine self-administration (e.g., responses, infusions, interinfusion intervals, consumption, and plasma levels), cardiovascular response (HR), and subjective effects (high) were observed. In contrast, cocaine-induced increases in other vital signs (e.g., SBP, DBP) and subjective effect measures (e.g., paranoia) did not differ between doses. Conclusions: These data support the safety, tolerability and validity of our single-day design. Depending on the application, such methods may afford advantages for assessing the self-regulation of cocaine administration behavior in humans (e.g., including medication development designs).
AB - Prior work by our group has shown the feasibility, safety, and validity of a multi-day, multi-dose paradigm of self-regulated cocaine administration in humans. The current work sought to consolidate these methods in a single-day design focused on reducing logistical complexity, decreasing research burden to human subjects, and increasing suitability for medication development designs. Methods: Eleven experienced cocaine users participated in a 6-hour, single-day design, consisting of one safety/eligibility and three experimental cocaine periods (during which subjects were allowed to self-administer 8, 16, and 32 mg/70 kg cocaine doses under a fixed-ratio 1:5 minute timeout schedule). Changes in cocaine-induced cardiovascular response, self-administration behavior, and subjective effects were assessed. Results: Procedures were well tolerated by participants, and no significant adverse events were noted. Significant (p < 0.05), changes in measures of cocaine self-administration (e.g., responses, infusions, interinfusion intervals, consumption, and plasma levels), cardiovascular response (HR), and subjective effects (high) were observed. In contrast, cocaine-induced increases in other vital signs (e.g., SBP, DBP) and subjective effect measures (e.g., paranoia) did not differ between doses. Conclusions: These data support the safety, tolerability and validity of our single-day design. Depending on the application, such methods may afford advantages for assessing the self-regulation of cocaine administration behavior in humans (e.g., including medication development designs).
KW - Cocaine plasma levels
KW - Cocaine self-administration
KW - Human studies
KW - Self-regulation
KW - Subjective effects
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U2 - 10.1016/j.pbb.2012.08.009
DO - 10.1016/j.pbb.2012.08.009
M3 - Article
C2 - 22922558
AN - SCOPUS:84865532902
SN - 0091-3057
VL - 103
SP - 95
EP - 101
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 1
ER -