- Email: [email protected]
Isolation rearing of rats produces a deficit in sensorimotor gating similar to that in schizophrenia
Influences on Neuronal and Receptor Development
BIOL PSYCHIATRY 1992;3! :61A-252A
197A
314 LONG-TERM NEUROBIOLOGICAL EFFECTS OF EARLY SOCIAL DEPRIVATION IN NONUMAN PRIMATES Mark H. Lewis, John P. Gluck, Linda L. Cork, Lee J. Martin, Richard B. Mailman University of North Cerolma, Chapel Hill, NC 27514. The behavioral effects of early social deprivation on nonhuman primates have been well documented. These effects include the development of high stereotyped behavior and marked alterations in social and affective functioning. We sought to determine the long-term neurobiological effects of such psychosocial insult. In vivo studies conducted with older adult monkeys suggest that early social deprivation results in long-term alterations in dopamine receptor function. Administration of the direct-acting dopamine agonist apomorphine significantly increased spontaneous blink rate and stereotyped behavior in experimental monkeys. These animals also demonstrated deficits in a sensory gating task. Early deprivation also results in long-term alterations in chemiarehitecture, as evidenced by significant reductions in markers for striatal dopaminergic neurons. These data provide important supl~rt for the hypothesis that early psychosocial insult can have long-term consequences on brain structure and function. These results are relevant to understanding the neuropsychiatric effects of early trauma.
315 ISOLATION REARING OF RATS PRODUCES A DEFICIT IN SENSORIMOTOR GATING SIMILAR TO THAT IN SCHIZOPHRENIA Mark A. Geyer, Lawrence S. Wilkinson, Trevor T. Humby, Trevor W. Robbins UCSD School of Medicine, La Jolla, CA 92093. Schizophrenic patients exhibit deficits in the prepulse inhibition (PPl) of startle, an operational measure of the sensorimotor gating deficits that may contribute to cognitive disorganization. In rats, the activation of mesolimbic dopamine (DA) disrupts PPl, providing a useful model of the similar deficits ill s,*,nsorimotor gating in schizophrenics. Rats reared in isolation exhibit neurochemicai and behavioral abnormalities suggestive of hyperactivity in mesolimbic DA systems. In the present studies, rats reared in social groups or in isolation were subjected to 120 dB acoustic pulses, some of which were preceded (100 msec) by prepulses that were 2, 4, 8, or 16 dB above the 65-dB background. Isolated al~imals were hyperreactive to the initial few startle stimuli, but were not different from socially reared animals in later trials. The amount of PPl was decreased significantly in isolated animals, particularly when 8-dB prepulses were used. A sut~sequent study replicated the effect of isolation on PPI and demonstrated that the deficit in PPl exhibited by isolated animals could be normalized by the administration of the DA antagonist raclopride (0.05 mg/kg). Hence, isolation rearing provides a nonpharmacological way to mimic in rats a deficit in sensorimotor gating that is exhibited by schizophrenics. This effect of isolation is sensitive to DA antagonists and has implications for possible developmental influences in schizophrenia. Supported by MH42228 and MH00188.
316 EFFECTS OF COCAINE ON DOPAMINE RECEPTOR AND NEUROPEPTIDE GENE EXPRESSION IN THE HUMAN BRAIN James H. Meador-Woodruff, Karley Y. Little, Scott P. Damask, Stanley J. Watson University of Michigan, Ann Arbor, MI, and University of North Carolina, Chapel Hill, NC. Cocaine is known to influence dopaminergic neurotransmission. The present study was desi~,ned to determine the effects of cocaine on the explession of genes encoding dopamine receptors as well as sev,. ~,~r~uropeptides known to be under dopaminergic regulation. The brains of nine subjects with a known his~'~ryof cocaine
BIOL PSYCHIATRY 1992;3! :61A-252A
197A
314 LONG-TERM NEUROBIOLOGICAL EFFECTS OF EARLY SOCIAL DEPRIVATION IN NONUMAN PRIMATES Mark H. Lewis, John P. Gluck, Linda L. Cork, Lee J. Martin, Richard B. Mailman University of North Cerolma, Chapel Hill, NC 27514. The behavioral effects of early social deprivation on nonhuman primates have been well documented. These effects include the development of high stereotyped behavior and marked alterations in social and affective functioning. We sought to determine the long-term neurobiological effects of such psychosocial insult. In vivo studies conducted with older adult monkeys suggest that early social deprivation results in long-term alterations in dopamine receptor function. Administration of the direct-acting dopamine agonist apomorphine significantly increased spontaneous blink rate and stereotyped behavior in experimental monkeys. These animals also demonstrated deficits in a sensory gating task. Early deprivation also results in long-term alterations in chemiarehitecture, as evidenced by significant reductions in markers for striatal dopaminergic neurons. These data provide important supl~rt for the hypothesis that early psychosocial insult can have long-term consequences on brain structure and function. These results are relevant to understanding the neuropsychiatric effects of early trauma.
315 ISOLATION REARING OF RATS PRODUCES A DEFICIT IN SENSORIMOTOR GATING SIMILAR TO THAT IN SCHIZOPHRENIA Mark A. Geyer, Lawrence S. Wilkinson, Trevor T. Humby, Trevor W. Robbins UCSD School of Medicine, La Jolla, CA 92093. Schizophrenic patients exhibit deficits in the prepulse inhibition (PPl) of startle, an operational measure of the sensorimotor gating deficits that may contribute to cognitive disorganization. In rats, the activation of mesolimbic dopamine (DA) disrupts PPl, providing a useful model of the similar deficits ill s,*,nsorimotor gating in schizophrenics. Rats reared in isolation exhibit neurochemicai and behavioral abnormalities suggestive of hyperactivity in mesolimbic DA systems. In the present studies, rats reared in social groups or in isolation were subjected to 120 dB acoustic pulses, some of which were preceded (100 msec) by prepulses that were 2, 4, 8, or 16 dB above the 65-dB background. Isolated al~imals were hyperreactive to the initial few startle stimuli, but were not different from socially reared animals in later trials. The amount of PPl was decreased significantly in isolated animals, particularly when 8-dB prepulses were used. A sut~sequent study replicated the effect of isolation on PPI and demonstrated that the deficit in PPl exhibited by isolated animals could be normalized by the administration of the DA antagonist raclopride (0.05 mg/kg). Hence, isolation rearing provides a nonpharmacological way to mimic in rats a deficit in sensorimotor gating that is exhibited by schizophrenics. This effect of isolation is sensitive to DA antagonists and has implications for possible developmental influences in schizophrenia. Supported by MH42228 and MH00188.
316 EFFECTS OF COCAINE ON DOPAMINE RECEPTOR AND NEUROPEPTIDE GENE EXPRESSION IN THE HUMAN BRAIN James H. Meador-Woodruff, Karley Y. Little, Scott P. Damask, Stanley J. Watson University of Michigan, Ann Arbor, MI, and University of North Carolina, Chapel Hill, NC. Cocaine is known to influence dopaminergic neurotransmission. The present study was desi~,ned to determine the effects of cocaine on the explession of genes encoding dopamine receptors as well as sev,. ~,~r~uropeptides known to be under dopaminergic regulation. The brains of nine subjects with a known his~'~ryof cocaine